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1
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Rx-ID: 43094965 Find similar reactions
With pyridine; nitrogen in diethyl ether; ethyl acetate; triethylamine
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University of Washington; Fred Hutchinson Cancer Research Center; Oricula Therapeutics LLC; SIMON, Julian; JOHNSON, Graham; RUBEL, Edwin; RAIBLE, David; GONZALEZ, Mario D.; MELTZER, Peter C.; MIAO, Weishi
Patent: US2016/229869 A1, 2016 ; Title/Abstract Full Text Show Details
1.2:Step 2:
Step 2: (5S)-methyl 8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate (3) To an oven-dried 2 L round bottom flask equipped with a magnetic stirring bar and nitrogen inlet was added at room temperature (20+-2° C.) compound 2 (41.5 g, 208 mmol) and anhydrous pyridine (414 mL) to form a dark red solution, which was then cooled in an ice-water bath with stirring for 30 minutes. To the above stirred solution was dropped in methanesulfonyl chloride (38.3 mL, 500 mmol) via a scaled addition funnel over 15 minutes. The resulting mixture was stirred for another 30 minutes with ice-water bath cooling. The ice-water bath was then removed and the reaction mixture was stirred at room temperature (20+-2° C.) under N2 for 48 hours. The reaction flask was again cooled in an ice-water bath for 25 minutes. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (156 mL, 1040 mmol) was dropped into the reaction mixture via a scaled addition funnel over 40 minutes. After addition finished, the stirring was continued for another 30 minutes. The ice-water bath was then removed and the reaction mixture was stirred at room temperature (20+-2° C.) under N for 24 hours.
2
The reaction mixture was carefully added to a 5 L round bottom flask charged with a magnetic stirring bar and diethyl ether (2.5 L) over 15 minutes with vigorously stirring. After addition finished, stirring was continued for another 10 min and then stopped. The mixture was left to stand for 40 min. The dark red ether phase was decanted out and the residue was washed with ether (350 mL*2). All the ether phases were combined and concentrated under reduced pressure (first used low vacuum to remove ether, then used high vacuum to remove most of pyridine) at water bath temperature<45° C. to give dark red oily residue (75 g) that was purified using Teledyne ISCO Combiflash automatic chromatography system (330 g Redisep silica gel column, Solvent A: 1percent Et3N/10percent MeOH/89percent EtOAc in Solvent B: 1percent Et3N/99percent EtOAc gradient) to give pure product 3 (26.3 g, 70percent) as a red oil, plus impure product 3 6.6 g; 1H-NMR (300 MHz, CDCl ) δ 6.82-6.78 (m, 1H, H-3), 3.76 (d, J=5.2 Hz, 1H, H-1), 3.72 (s, 3H, OCH ), 3.22 (t, J=5.5 Hz, 1H, H-5), 2.61 (d, J=19.5 Hz, 1H, H-4 ), 2.33 (s, 3H, NCH ), 2.213 3 ax 3
2.06 (m, 2H), 1.89-1.70 (m, 2H), 1.54-1.41 (m, 1H); CIMS [M+1]+182.
2
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Rx-ID: 1679820 Find similar reactions
95%
With sodium cyanoborohydride in water; acetonitrile
0.25 h;
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Davies; Saikali; Young
Journal of Organic Chemistry, 1991 , vol. 56, # 19 p. 5696 - 5700 Title/Abstract Full Text View citing articles Show Details
3
Synthesize Find similar Multi-step reaction with 5 steps 1: 1.) lithium diisopropylamide, HMPA, 2.) ptoluenesulfonyl azide / 1.) ether, hexane, -78 deg C, 30 min, 2.) -78 deg C to r.t., 12 h 2: 62 percent / rhodium(II) hexanoate / hexane / 12 h / Heating 3: 92 percent / hydrogen / RhCl(PPh3)3 / ethanol / 12 h / 2327.2 Torr 4: 95 percent / 1 M tetrabutylammonium fluoride / tetrahydrofuran / 12 h / Ambient temperature 5: 95 percent / sodium cyanoborohydride / acetonitrile; H2O / 0.25 h View Scheme
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Rx-ID: 21028325 Find similar reactions
Davies; Saikali; Young
Journal of Organic Chemistry, 1991 , vol. 56, # 19 p. 5696 - 5700 Title/Abstract Full Text View citing articles Show Details
4
Synthesize Find similar Multi-step reaction with 4 steps 1: 62 percent / rhodium(II) hexanoate / hexane / 12 h / Heating 2: 92 percent / hydrogen / RhCl(PPh3)3 / ethanol / 12 h / 2327.2 Torr 3: 95 percent / 1 M tetrabutylammonium fluoride / tetrahydrofuran / 12 h / Ambient temperature 4: 95 percent / sodium cyanoborohydride / acetonitrile; H2O / 0.25 h View Scheme
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Rx-ID: 21037925 Find similar reactions
Davies; Saikali; Young
Journal of Organic Chemistry, 1991 , vol. 56, # 19 p. 5696 - 5700 Title/Abstract Full Text View citing articles Show Details
5
Synthesize Find similar Multi-step reaction with 3 steps 1: 92 percent / hydrogen / RhCl(PPh3)3 / ethanol / 12 h / 2327.2 Torr 2: 95 percent / 1 M tetrabutylammonium fluoride / tetrahydrofuran / 12 h / Ambient temperature 3: 95 percent / sodium cyanoborohydride / acetonitrile; H2O / 0.25 h View Scheme
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Rx-ID: 21049429 Find similar reactions
Davies; Saikali; Young
Journal of Organic Chemistry, 1991 , vol. 56, # 19 p. 5696 - 5700 Title/Abstract Full Text View citing articles Show Details
6
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Rx-ID: 3825187 Find similar reactions
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150 mg
With sulfuric acid
24 h; Heating; Yield given;
Kline Jr.; Wright; Fox; Eldefrawi
Journal of Medicinal Chemistry, 1990 , vol. 33, # 7 p. 2024 - 2027 Title/Abstract Full Text View citing articles Show Details
T=-40 - 20°C; Esterification; 0.333333 h;
Hoepping; George; Flippen-Anderson; Kozikowski
Tetrahedron Letters, 2000 , vol. 41, # 39 p. 7427 - 7432 Title/Abstract Full Text View citing articles Show Details
With sulfuric acid
48 h; Heating;
Wyatt, Emma E.; Fergus, Suzanne; Galloway, Warren R. J. D.; Bender, Andreas; Fox, David J.; Plowright, Alleyn T.; Jessiman, Alan S.; Welch, Martin; Spring, David R.
Chemical Communications, 2006 , # 31 p. 3296 - 3298 Title/Abstract Full Text View citing articles Show Details
7
Synthesize Find similar Multi-step reaction with 2 steps 1: 95 percent / 1 M tetrabutylammonium fluoride / tetrahydrofuran / 12 h / Ambient temperature 2: 95 percent / sodium cyanoborohydride / acetonitrile; H2O / 0.25 h View Scheme
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Rx-ID: 21049437 Find similar reactions
Davies; Saikali; Young
Journal of Organic Chemistry, 1991 , vol. 56, # 19 p. 5696 - 5700 Title/Abstract Full Text View citing articles Show Details
8
Synthesize Find similar Multi-step reaction with 2 steps 1: aq. NaOH / 6 h / 150 °C / 103430 Torr 2: concd H2SO4 / 24 h / Heating View Scheme
9
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Rx-ID: 21901386 Find similar reactions
Kline Jr.; Wright; Fox; Eldefrawi
Journal of Medicinal Chemistry, 1990 , vol. 33, # 7 p. 2024 - 2027 Title/Abstract Full Text View citing articles Show Details
Synthesize Find similar Multi-step reaction with 2 steps 1: POCl3 / 4 h / Heating 2: 0.33 h / -40 - 20 °C View Scheme
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Rx-ID: 15686934 Find similar reactions
Hoepping; George; Flippen-Anderson; Kozikowski
Tetrahedron Letters, 2000 , vol. 41, # 39 p. 7427 - 7432 Title/Abstract Full Text View citing articles Show Details
10
Synthesize Find similar Multi-step reaction with 3 steps 1: aq. HCl / 16 h / Heating 2: POCl3 / 4 h / Heating 3: 0.33 h / -40 - 20 °C View Scheme
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Rx-ID: 15709786 Find similar reactions
Hoepping; George; Flippen-Anderson; Kozikowski
Tetrahedron Letters, 2000 , vol. 41, # 39 p. 7427 - 7432 Title/Abstract Full Text View citing articles Show Details
11
Synthesize Find similar 46%
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Rx-ID: 5444300 Find similar reactions
Okano, Kyoko; Itoh, Osamu
Patent: US2001/20096 A1, 2001 ; Title/Abstract Full Text Show Details
2:Example 2
Example 2 Synthesis of methyl (1RS)-8-methyl-8-azabicyclo[ 3.2.1]oct-2-ene-2-carboxylate (7:
(1RS)-AECG; dl-anhydroecgonine methyl ester) In 2.3 ml of 95percent methanol solution was dissolved 0.727 g (4.91 mmol) of the (1RS)-AECG-CN synthesised in Example 1, followed by adding thereto 1.2 ml of concentrated sulfuric acid, and the resulting mixture was stirred with heating at 110° C. for 6 hours. After completion of the reaction, the methanol was evaporated and the residue was neutralized with saturated sodium hydrogencarbonate solution, followed by extraction with ethyl acetate. The organic layer was dried and then distilled to remove the solvent, whereby 0.41 g of (1RS)-AECG was obtained as a brown oil (yield: 46percent). Zirkle et al.
Journal of Organic Chemistry, 1962 , vol. 27, p. 1269,1277 Full Text Show Details
Clarke et al.
Journal of Medicinal Chemistry, 1973 , vol. 16, p. 1260,1262 Title/Abstract Full Text Show Details
11 reactions out of 1 substances and 8 citations
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