N-benzyloxycarbonyl-3-pyrrolidinone-syns

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Date

12 reactions in Reaxys

2017-11-12 20h:26m:51s (EST)

O

1. Query

O

N

O

Search as: Product, As drawn

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O

N

O

OH

Rx-ID: 3091249 View in Reaxys 1/12 Yield 96 %

Conditions & References 6.6.iv :6.iv. 3 -oxo-pyrrolidine- 1-carboxylic acid benzyl ester:A solution of intermediate .iii (1.10 g) in DCM (8 ml) was cooled to 0 0C and DIPEA (2.5 ml) was added dropwise, followed by a solution of sulfur trioxide pyridine complex (1.79 g) in DMSO (6.5 ml). The reaction mixture was stirred at 0 0C for 1 h and was quenched by the addition of water (6 ml). The aq. layer was extracted with Et2O/Hex (1 :1, 3 x 5 ml) and the combined org. layers were concentrated in vacuo. The residue obtained after work up (Et2O/Hex 1 :1) was purified by chromatography (Hex/EA 5:5) to give 1.05 g (96percent yield) of a yellowish oil. 1H NMR (DMSOd6; δ ppm): 2.48-2.61 (2H, m); 3.61-3.80 (4H, m); 5.09 (2H, s); 7.27-7.41 (5H, m). Stage 1: With pyridine-SO3 complex, N-ethyl-N,N-diisopropylamine in dichloromethane, dimethyl sulfoxide, Time= 1h, T= 0 °C Stage 2: With water in dichloromethane, dimethyl sulfoxide Patent; ACTELION PHARMACEUTICALS LTD; WO2008/56335; (2008); (A1) English View in Reaxys

96%

6.6.iv :A solution of intermediate 6.iii (1.10 g) in DCM (8 mL) was cooled to 0° C. and DIPEA (2.5 mL) was added dropwise, followed by a solution of sulfur trioxide pyridine complex (1.79 g) in DMSO (6.5 mL). The reaction mixture was stirred at 0° C. for 1 h and was quenched by the addition of water (6 mL). The aq. layer was extracted with Et2O/Hex (1:1, 3*5 mL) and the combined org. layers were concentrated in vacuo. The residue obtained after work up (Et2O/Hex 1:1) was purified by chromatography (Hex/EA 5:5) to give 1.05 g (96percent yield) of a yellowish oil. 1H NMR (DMSO ; δ ppm): 2.48-2.61 (2H, m); 3.61-3.80 (4H, m); 5.09 (2H, s); 7.27-7.41 (5H, m). d6 With sulfur trioxide pyridine complex, N-ethyl-N,N-diisopropylamine in dichloromethane, dimethyl sulfoxide, T= 0 °C Patent; Actelion Pharmaceuticals Ltd.; US2009/247578; (2009); (A1) English View in Reaxys

90 %

7.C : Synthesis of C To a stirred solution of intermediate B (15.50 g, 0.07 mol) in DCM (100 mL) was added DIPEA (35.2 mL 0.21 mol) at 0°C . A solution of pyridine sulfur trioxide (25.2g, 0.16 mol) in DMSO (70 mL) was added dropwise and the resulting mixture stirred at 0°C for 1 h. The reaction was quenched by addition of H20 and the aqueous layer was extracted twice with DCM. The combined organic layers were washed with brine, dried (Na2S04), filtered and concentrated. The crude product obtained was purified by flash chromatography (EtOAc/Pet ether=1 :2) to give compound C (13.80 g, 90percent) as yellow solid. It's structure was confirmed by LC-MS spectra. TLC:Rf=0.7(silica gel,EA:PE=1 : 1 , v/v) LC-MS :[M+23]= 242. With sulfur trioxide pyridine complex, dimethyl sulfoxide, N-ethyl-N,N-diisopropylamine in dichloromethane, Time= 1h, T= 0 °C Patent; YM BIOSCIENCES AUSTRALIA PTY LTD; BURNS, Christopher John; WO2014/32; (2014); (A1) English View in Reaxys

86 %

With sodium hypochlorite, potassium hydrogencarbonate, potassium bromide, poly(vinyl alcohol)-graft-poly(ethylene glycol) TEMPO resin in dichloromethane, Time= 0.5h, T= 20 °C , pH= 9.1 Luo, Juntao; Pardin, Christophe; Lubell, William D.; Zhu; Chemical Communications; nb. 21; (2007); p. 2136 2138 View in Reaxys

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27 %

13.18 :Benzyl 3-hydroxypyrrolidine-1-carboxylate (0.30 g, 1.34 mmol) was dissolved in DCM (20 mL) and pyridinium chlorochromate was added (0.44 g, 2.0 mmol). The resulting slurry was stirred at room temperature for 72 h. Benzyl 3-oxopyrrolidine-1-carboxylate (0.080 g, 27percent) was isolated as a colorless oil by prep. HPLC YMC ODSA 30.x. 100 mm, 20-100percent MeOH/H2O (0.1percent TFA) gradient over 10 mins at 20 mL/min flow rate at a retention time of 4.25 min. LCMS: 1.20 min [M+1] not observed (2 min gradient, MeOH/H2O 0.1percent TFA). With pyridinium chlorochromate in dichloromethane, Time= 72h, T= 20 °C Patent; Bristol-Myers Squibb Company; US2007/161685; (2007); (A1) English View in Reaxys

5.6 %

With oxalyl dichloride, dimethyl sulfoxide, triethylamine in dichloromethane, T= -60 - 20 °C , Swern oxidation Plouvier, Bertrand; Beatch, Gregory N.; Jung, Grace L.; Zolotoy, Alexander; Sheng, Tao; Clohs, Lilian; Barrett, Terrance D.; Fedida, David; Wang, Wei Q.; Zhu, Jeff J.; Liu, Yuzhong; Abraham, Shlomo; Lynn, Leah; Dong, Ying; Wall, Richard A.; Walker, Michael J. A.; Journal of Medicinal Chemistry; vol. 50; nb. 12; (2007); p. 2818 - 2841 View in Reaxys

5.6 %

15.ii : EXAMPLE 15(1R,2R)/(1S,2S)-2-(3-KETOPYRROLIDINYL)-1-(1-NAPHTHENETHOXY)CYCLOHEXANE MONOHYDROCHLORIDE (COMPOUND No.15) (ii) N-Benzyloxycarbonyl-3-pyrrolidinone: To a chilled (-60°C) solution of oxalyl chloride (23 mL, 98percent, 258.6 mmol) in dichloromethane (400 mL) was added dropwise a solution of anhydrous dimethyl sulfoxide (36.7 mL, 517.3 mmol) in dichloromethane (20 mL) at such a rate to keep the temperature below -40°C. The reaction mixture was then stirred at -60°C for 15 min. Then a solution of N-benzyloxycarbonyl-3-pyrrolidinol (58.22 g, step i, no more than 224.9 mmol) in dichloromethane (80 mL) was added dropwise, keeping the reaction mixture temperature below -50°C. The reaction mixture was then stirred at -60°C for 30 min before adding triethylamine (158.3 mL, 99percent, 1.125 mol). The resulting mixture was allowed to warm up to room temperature and then washed with water (600 mL), 1M HCl aqueous solution (580 mL) and water (400 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to leave 54.5 g of amber oil, which was further pumped under high vacuum with stirring at room temperature for 25 min. to give 52.08 g (5.6percent over theoretical yield) of the crude title compound suitable for the next step without any further purification. Stage 1: With oxalyl dichloride, dimethyl sulfoxide in dichloromethane, Time= 0.5h, T= -60 - -50 °C Stage 2: With triethylamine, T= 20 °C Patent; Nortran Pharmaceuticals Inc.; EP1087934; (2004); (B1) English View in Reaxys With sulfur trioxide pyridine complex, triethylamine in dimethyl sulfoxide, Time= 1h, T= 0 °C Cooper, Curt S.; Klock, Pamela L.; Chu, Daniel T. W.; Hardy, Dwight J.; Swanson, Robert N.; Plattner, Jacob J.; Journal of Medicinal Chemistry; vol. 35; nb. 8; (1992); p. 1393 - 1398 View in Reaxys 66.b : 3-Cyano-3-{3-cyclohexyl-2-[(morpholine-4-carbonyl)-amino]-propionylamino}-pyrrolidine-1-carboxylic acid benzyl ester. After addition, the mixture was stirred for an additional 25 min and then a solution of 3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester (11 g, 50 mmol, 1.0 equiv) in 20 mL of CH2Cl2 was added dropwise over a 10 min period. After complete addition the reaction was stirred an additional a hour at -78° C. Et 3N (55 mL, 398 mmol, 8.0 equiv) was added over a period of 10 min. The cold-bath was removed and the mixture was stirred while warming for 2 h. The mixture was diluted with 500 mL of water. After thorough mixing, the layers were separated and the aqueous layer was extracted 2xl50 mL of CH 2Cl2. The combined organic layers were washed with 200 mL of sodium bicarbonate solution and 200 mL of brine, dried over Na2SO4, decanted, and concentrated to a yellow oil. The product was purified by flash chromatography on silica gel using CH2Cl2 as eluent to yield the desired product as a colorless oil (8.5 g). With triethylamine in dichloromethane, water Patent; Emmanuel, Michel Jose; Hickey, Eugene R.; Liu, Weimin; Spero, Denice Mary; Sun, Sanxing; Thomson, David S.; Ward, Yancey David; Young, Erick Richard Roush; US2002/58809; (2002); (A1) English

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View in Reaxys 82 : Reference Example 82 Reference Example 82 A mixture of benzyl 3-hydroxy-1-pyrrolidine carboxylate (10.0 g), pyridinium nichromate (14.6 g), and dichloromethane (150 mL) was stirred at room temperature for 3 days. Insolubles were filtered off using celite and washed with dichloromethane. Mother liquor was concentrated, and the obtained residue was purified by silica gel column chromatography to obtain benzyl 3-oxo-1-pyrrolidine carboxylate (4.39 g). 1H-NMR (300 MHz, CDCl ) δ: 2.61 (2H, t, J=7.5 Hz), 3.83-3.89 (4H, m), 5.18 (2H, s), 7.33-7.39 (5H, m). 3 With dipyridinium dichromate in dichloromethane, Time= 72h, T= 20 °C Patent; Takeda Pharmaceutical Company Limited; EP1553074; (2005); (A1) English View in Reaxys

N

O N

O

O N H

O

N

O

Rx-ID: 5217917 View in Reaxys 2/12 Yield

Conditions & References

62 %

With copper acetylacetonate in benzene, Time= 1.5h, Heating, Cyclization Wang, Jianbo; Hou, Yihua; Wu, Peng; Journal of the Chemical Society - Perkin Transactions 1; nb. 16; (1999); p. 2277 - 2280 View in Reaxys

O

N

O

OH

Rx-ID: 9537012 View in Reaxys 3/12 Yield

Conditions & References With oxalyl dichloride, dimethyl sulfoxide, triethylamine in dichloromethane, Swern oxidation Caldwell, Charles G.; Chen, Ping; He, Jiafang; Parmee, Emma R.; Leiting, Barbara; Marsilio, Frank; Patel, Reshma A.; Wu, Joseph K.; Eiermann, George J.; Petrov, Aleksandr; He, Huaibing; Lyons, Kathryn A.; Thornberry, Nancy A.; Weber, Ann E.; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 5; (2004); p. 1265 - 1268 View in Reaxys 2.A :A 12-L, 3 neck round bottom flask equipped with a mechanical stirrer, thermocouple, condenser, and nitrogen bubbler was charged with 351 g (1.61 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate (Intermediate 1, Step A), 6 L of dichloromethane, 500 g of powdered molecular sieves, and 400 g (3.41 mol) of N-methylmorpholine-Noxide. The resultant suspension was stirred at ambient temperature and to this was added 12.9 g (0.0367 mol) of tetrapropylammonium perruthenate. The reaction temperature was kept at or below 30 °C with a cold water bath. The mixture was stirred at ambient temperature for 2 h. The mixture was poured onto a plug of 5 kg of silica gel and eluted with 10percent ethyl acetate/dichloromethane to give the title compound as an orange oil. With tetrapropylammonium perruthennate, 4-methylmorpholine N-oxide in dichloromethane, Time= 2h, T= 20 - 30 °C Patent; MERCK and CO., INC.; WO2005/44195; (2005); (A2) English View in Reaxys 3.A : 3, 3-DIFLUOROPYRROLIDINE hydrochloride; Step A: Benzyl 3-oxopyrrolidine-l-carboxylate A 12-L, 3 neck round bottom flask equipped with a mechanical stirrer, thermocouple, condenser, and nitrogen bubbler was charged with 351 g (1.61 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate (Intermediate 1, Step A), 6

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L of dichloromethane, 500 g of powdered molecular sieves, and 400 g (3. 41 mol) of N-methylmorpholine-N-oxide. The resultant suspension was stirred at ambient temperature and to this was added 12.9 g (0.0367 mol) of tetrapropylammonium perruthenate. The reaction temperature was kept at < 30 °C with a cold water bath. The mixture was stirred at ambient temperature for 2 h. The mixture was poured onto a plug of 5 kg of silica gel and eluted with 10percent ethyl ACETATE/DICHLOROMETHANE to give the title compound as an orange oil. With tetrapropylammonium perruthennate, 4-methylmorpholine N-oxide in dichloromethane, Time= 2h, T= 20 - 30 °C , Molecular sieves Patent; MERCK and CO., INC.; WO2004/43940; (2004); (A1) English View in Reaxys A :A 12-L, 3 neck round bottom flask equipped with a mechanical stirrer, thermocouple, condenser, and nitrogen bubbler was charged with 351 g (1.61 mol) of benzyl (3R)-3-hydroxypyrrolidine- 1-carboxylate (Intermediate 1, Step A), 6 L of dichloromethane, 500 g of powdered molecular sieves, and 400 g (3.41 mol) of N-methylmorpholine-Noxide. The resultant suspension was stirred at ambient temperature and to this was added 12.9 g (0.0367 mol) of tetrapropylammonium perruthenate. The reaction temperature was kept at < 30 °C with a cold water bath. The mixture was stirred at ambient temperature for 2 h. The mixture was poured onto a plug of 5 kg of silica gel and eluted with 10percent ethyl acetate/dichloromethane to give the title compound as an orange oil. With 4-methylmorpholine N-oxide, tetrapropylammonium perruthennate in dichloromethane, Time= 2h, T= 20 - 30 °C , Molecular sieve Patent; MERCK and CO., INC.; WO2005/108382; (2005); (A1) English View in Reaxys 3.A :INTERMEDIATE 3; 3,3-Difluoropyrrolidine hydrochloride Step A: Benzyl 3-oxopyrrolidine-1-carboxylate A 12-L, 3 neck round bottom flask equipped with a mechanical stirrer, thermocouple, condenser, and nitrogen bubbler was charged with 351 g (1.61 mol) of benzyl (3R)-3- hydroxypyrrolidine-1-carboxylate (Intermediate 1, Step A), 6 L of dichloromethane, 500 g of powdered molecular sieves, and 400 g (3.41 mol) of N-methylmorpholine-N-oxide. The resultant suspension was stirred at ambient temperature and to this was added 12.9 g (0.0367 mol) of tetrapropylammonium perruthenate. The reaction temperature was kept at < 30 °C with a cold water bath. The mixture was stirred at ambient temperature for 2 h. The mixture was poured onto a plug of 5 kg of silica gel and eluted with 10percent ethyl acetate/dichloromethane to give the title compound as an orange oil. With tetrapropylammonium perruthennate, 4-methylmorpholine N-oxide in dichloromethane, Time= 2h, T= 20 - 30 °C Patent; MERCK and CO., INC.; WO2005/116029; (2005); (A1) English View in Reaxys O O

O

/PXPAB263-1160/

O

N

Cl

O

Rx-ID: 11471245 View in Reaxys 4/12 Yield

Conditions & References Reaction Steps: 2 1: 17 percent / Et3N / CH2Cl2 / -60 - 20 °C 2: 5.6 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -60 - 20 °C With oxalyl dichloride, dimethyl sulfoxide, triethylamine in dichloromethane, 2: Swern oxidation Plouvier, Bertrand; Beatch, Gregory N.; Jung, Grace L.; Zolotoy, Alexander; Sheng, Tao; Clohs, Lilian; Barrett, Terrance D.; Fedida, David; Wang, Wei Q.; Zhu, Jeff J.; Liu, Yuzhong; Abraham, Shlomo; Lynn, Leah; Dong, Ying; Wall, Richard A.; Walker, Michael J. A.; Journal of Medicinal Chemistry; vol. 50; nb. 12; (2007); p. 2818 - 2841 View in Reaxys Reaction Steps: 2 1: 98 percent / Na2CO3 / diethyl ether; H2O 2: 86 percent / bleach; KHCO3; KBr / poly(vinyl alcohol)-graft-poly(ethylene glycol) TEMPO resin / CH2Cl2 / 0.5 h / 20 °C / pH 9.1

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With sodium hypochlorite, sodium carbonate, potassium hydrogencarbonate, potassium bromide, poly(vinyl alcohol)-graft-poly(ethylene glycol) TEMPO resin in diethyl ether, dichloromethane, water Luo, Juntao; Pardin, Christophe; Lubell, William D.; Zhu; Chemical Communications; nb. 21; (2007); p. 2136 2138 View in Reaxys O

O

HO

N H

O

N

O

Rx-ID: 16172006 View in Reaxys 5/12 Yield

Conditions & References Reaction Steps: 2 1.1: RO-CO-Cl (R = Bn or i-Bu); Et3N / diethyl ether; tetrahydrofuran / 0.5 h / -20 °C 1.2: diethyl ether; tetrahydrofuran / 4 h / -10 - 20 °C 2.1: 62 percent / Cu(acac)2 / benzene / 1.5 h / Heating With copper acetylacetonate, RO-CO-Cl (R = Bn or i-Bu), triethylamine in tetrahydrofuran, diethyl ether, benzene, 1.1: Acylation / 1.2: Acylation / 2.1: Cyclization Wang, Jianbo; Hou, Yihua; Wu, Peng; Journal of the Chemical Society - Perkin Transactions 1; nb. 16; (1999); p. 2277 - 2280 View in Reaxys O

O

Cl

O

N

O O

Rx-ID: 20250627 View in Reaxys 6/12 Yield

Conditions & References Reaction Steps: 2 1: 94 percent / 1 M aq. NaOH / diethyl ether / 3 h 2: pyridine-SO3, Et3N / dimethylsulfoxide / 1 h / 0 °C With sodium hydroxide, sulfur trioxide pyridine complex, triethylamine in diethyl ether, dimethyl sulfoxide Cooper, Curt S.; Klock, Pamela L.; Chu, Daniel T. W.; Hardy, Dwight J.; Swanson, Robert N.; Plattner, Jacob J.; Journal of Medicinal Chemistry; vol. 35; nb. 8; (1992); p. 1393 - 1398 View in Reaxys

O Cl

O

Cl

O

N

O

OH

Rx-ID: 24198194 View in Reaxys 7/12 Yield 20.1 g (86%)

Conditions & References A : 1-Benzyloxycarbonyl-3-pyrrolidone Example A 1-Benzyloxycarbonyl-3-pyrrolidone A dichloromethane (40 ml) solution of 16.58 ml (233.6 mmol) of dimethyl sulfoxide was added dropwise to a dichloromethane (200 ml) solution of 10.19 ml (116.8 mmol) of oxalyl chloride at -78° C., and the mixture was stirred for 10 minutes at the same temperature. To the reaction solution was added dropwise a solution of 23.50 g of literary known 1-benzyloxycarbonyl-3-hydroxypyrrolidine in 200 ml of dichloromethane at -78° C., followed by 60 minutes of stirring at the same temperature. This solution was mixed with 74.02 ml (531.1 mmol) of triethylamine at -78° C., and stirred for 60 minutes at the same temperature and then at room temperature for 60 minutes.

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After completion of the reaction, 500 ml of water was added dropwise to the reaction solution, and the organic layer was separated. The aqueous layer was washed with dichloromethane (100 ml*2), and combined organic layer was washed with saturated brine (300 ml*1). After drying the organic layer over sodium sulfate, the solvent was evaporated. The resulting residue was subjected to a silica gel column chromatography to yield 20.1 g (86percent) of the title compound as an oily product from the elude of n-hexane:ethyl acetate=1:1. 1H-NMR (400 MHz, CDCl ) δ: 2.58-2.62 (2H, m), 3.82-3.87 (4H, m), 5.18 (2H, s), 7.30-7.37 (5H, m). 3 With dimethyl sulfoxide, triethylamine in dichloromethane, water Patent; Daiichi Pharmaceutical Co., Ltd.; US6469023; (2002); (B1) English View in Reaxys O O

N

O

Rx-ID: 24392818 View in Reaxys 8/12 Yield

Conditions & References

74 %

17 Patent; PFIZER PRODUCTS INC.; WO2007/60526; (2007); (A1) English View in Reaxys P.36 : N-(Benzyloxycarbonyl)-3-pyrrolidone STR246 Preparatory Example 36 N-(Benzyloxycarbonyl)-3-pyrrolidone STR246 150 ml of oxalic acid chloride was added to 2 liters of dichloromethylene. 245 ml of dimethylsulfoxide was gradually added at -70° to -50° C. in a stream of argon. 70.67 g of N-(N-(benzyloxycarbonyl)-3-pyrrolidinol dissolved in dichloromethylene was dropped. After gradual dropping of 720 ml of triethylamine, the mixture was raised to room temperature. After completion of the reaction, the reaction solution was poured into water and extracted with dichloromethylene, followed by removal of the solvent by distillation under reduced pressure. The residue was purified by column chromatography (eluding solvent: hexane-ethyl acetate), thereby obtaining 66.55 g of the intended compound. 1 H-NMR(90 MHz, CDCl ) δ:2.6(t,J=7.5 Hz,2H), 3.7-4.0(m,4H), 5.12(s,2H), 7.3(s,5H) 3 Patent; Eisai Co., Ltd.; US5221671; (1993); (A1) English View in Reaxys

N+

O Ru – O O

O

N

O

N

(v8)

O

N

O

OH

Rx-ID: 25517236 View in Reaxys 9/12 Yield

Conditions & References 41.B : Preparation of (+/-)-N-phenyl-3-[[4-[(4-fluorophenyl)methyl]-1-piperidinyl]methyl]-1-pyrrolidinecarboxamide Part B. Preparation of N-(benzyloxycarbonyl)-3-pyrrolidinone. To a stirring solution of N-(benzyloxycarbonyl)-3-pyrrolidinol (1600 mg, 7.2 mmol) and 4-methylmorpholine oxide (1269 mg, 10.8 mmol, Aldrich) in dry CH2Cl2 (100 mL) with activated molecular sieves (1000 mg) was added tetrapropylammonium perruthenate (127 mg, 0.36 mmol, Aldrich). The reaction was stirred for 1 h and then filtered through a pad of silica gel. The silica gel was washed with EtOAc (500 mL). The organic filtrates were combined and conc.

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in vacuo to a colorless oil of pure N-(benzyloxycarbonyl)-3-pyrrolidinone. MS (ESI) 220 (M+H). With silica gel in dichloromethane Patent; Ko, Soo S.; DeLucca, George V.; Duncia, John V.; Santella, III, Joseph B.; Wacker, Dean A.; US6331545; (2001); (B1) English View in Reaxys

O

N

N O

O

O O

Rx-ID: 28193923 View in Reaxys 10/12 Yield

Conditions & References With hydrogenchloride in water Jung, Myung-Ho; Joon, Hee Hong; Cho, Jung-Hyuck; Oh, Chang-Hyun; Archiv der Pharmazie; vol. 341; nb. 12; (2008); p. 780 - 786 View in Reaxys O

O

N

O Cl

O

Rx-ID: 37011938 View in Reaxys 11/12 Yield

Conditions & References Reaction Steps: 2 1: sodium carbonate / water; tetrahydrofuran / 1 h / 20 °C 2: N-ethyl-N,N-diisopropylamine; sulfur trioxide pyridine complex; dimethyl sulfoxide / dichloromethane / 1 h / 0 °C With sulfur trioxide pyridine complex, sodium carbonate, dimethyl sulfoxide, N-ethyl-N,N-diisopropylamine in tetrahydrofuran, dichloromethane, water Patent; YM BIOSCIENCES AUSTRALIA PTY LTD; BURNS, Christopher John; WO2014/32; (2014); (A1) English View in Reaxys Reaction Steps: 2 1: triethylamine / dichloromethane / 48 h / 5 - 20 °C 2: 4-methylmorpholine N-oxide; tetrapropylammonium perruthennate / dichloromethane / 2 h / |Molecular sieve; |Inert atmosphere With tetrapropylammonium perruthennate, 4-methylmorpholine N-oxide, triethylamine in dichloromethane Patent; PFIZER INC.; SPRINGER, John Robert; DEVADAS, Balekudru; GARLAND, Danny James; GRAPPERHAUS, Margaret Lanahan; HAN, Seungil; HOCKERMAN, Susan Landis; HUGHES, Robert Owen; SAIAH, Eddine; SCHNUTE, Mark Edward; SELNESS, Shaun Raj; WALKER, Daniel Patrick; WAN, Zhao-Kui; XING, Li; ZAPF, Christoph Wolfgang; SCHMIDT, Michelle, Ann; WO2014/68527; (2014); (A1) English View in Reaxys

O

O N

O

N

O

OH

Rx-ID: 37783074 View in Reaxys 12/12

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Yield 88 %

Conditions & References 7.2 : Step 2: preparation of benzyl 3-oxopyrrolidine-1-carboxylate. Step 2: preparation of benzyl 3-oxopyrrolidine-1-carboxylate. To a solution ofbenzyl (3S)-3-hydroxypyrrolidine-1-carboxylate (7.5 g, 33.9 mmol) in dichloromethane(1.2 L) was added 4-methylmorpholine N-oxide (5.96 g, 50.0 mmol), tetrapropylammonium perruthenate (0.60 g, 1 .7 mmol), and 4 A molecular sieves (7.0 g). The reaction mixture was allowed to stir under nitrogen for 2 h, after which it was filtered through a silica gel plug and eluted with diethyl ether. The filtrate canconcentrated to afford the title compound as clear oil (6.5 g, 88percent). With tetrapropylammonium perruthennate, 4-methylmorpholine N-oxide in dichloromethane, Time= 2h, Molecular sieve, Inert atmosphere Patent; PFIZER INC.; SPRINGER, John Robert; DEVADAS, Balekudru; GARLAND, Danny James; GRAPPERHAUS, Margaret Lanahan; HAN, Seungil; HOCKERMAN, Susan Landis; HUGHES, Robert Owen; SAIAH, Eddine; SCHNUTE, Mark Edward; SELNESS, Shaun Raj; WALKER, Daniel Patrick; WAN, Zhao-Kui; XING, Li; ZAPF, Christoph Wolfgang; SCHMIDT, Michelle, Ann; WO2014/68527; (2014); (A1) English View in Reaxys

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