1-Phenylcyclohexanamine [C12H17N]

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26 reactions in Reaxys

2017-12-10 12h:06m:47s (EST)

H 2N

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O

N

H 2N

O

Rx-ID: 365781 View in Reaxys 1/26 Yield

Conditions & References

90 %

With sodium dithionite, potassium carbonate, N,N'-dioctyl-4,4'-bipyridinium in water, acetonitrile, Time= 24h, T= 35 °C Park, Kwanghee Koh; Oh, Chang Hun; Sim, Woo-Jeon; Journal of Organic Chemistry; vol. 60; nb. 19; (1995); p. 6202 - 6204 View in Reaxys With hydrogenchloride, tin Kurssanow; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 38; (1906); p. 1300; Chem. Zentralbl.; vol. 78; nb. I; (1907); p. 1744 View in Reaxys

O

H 2N

Cl

Rx-ID: 968793 View in Reaxys 2/26 Yield

Conditions & References (i) NaN3, xylene, (ii) aq. HCl, Multistep reaction Bonnekessel,J.; Ruechardt,C.; Chemische Berichte; vol. 106; (1973); p. 2890 - 2903 View in Reaxys (i) NaN3, toluene, (ii) aq. HCl, toluene, Multistep reaction Carissimi; D'Ambrosio; Grumelli; Milla; Ravenna; Il Farmaco; edizione scientifica; vol. 21; nb. 2; (1966); p. 155 171 View in Reaxys Reaction Steps: 3 1: aq. NH3 2: Br2 / methanol 3: KOH / bis-(2-hydroxy-ethyl) ether With potassium hydroxide, ammonium hydroxide, bromine in methanol, diethylene glycol Kalir,A.; Pelah,K.; Israel Journal of Chemistry; vol. 5; (1967); p. 223 - 229 View in Reaxys

O OH

H 2N

Rx-ID: 978885 View in Reaxys 3/26 Yield 66 %

Conditions & References Stage 1: With diphenyl phosphoryl azide, triethylamine in toluene, Time= 2h, T= 90 °C , Inert atmosphere, Reflux Stage 2: With hydrogenchloride in water, Reflux Weinstein, Adam B.; Ellman, Jonathan A.; Organic Letters; vol. 18; nb. 13; (2016); p. 3294 - 3297 View in Reaxys (i) aq. NaN3, ClCO2Et, Et3N, acetone, (ii) toluene, (iii) aq. HCl, Multistep reaction Palmere,R.M.; Conley,R.T.; Journal of Organic Chemistry; vol. 35; (1970); p. 2703 - 2707 View in Reaxys

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Reaction Steps: 2 1: SOCl2 / Heating 2: (i) NaN3, toluene, (ii) aq. HCl, toluene With thionyl chloride Carissimi; D'Ambrosio; Grumelli; Milla; Ravenna; Il Farmaco; edizione scientifica; vol. 21; nb. 2; (1966); p. 155 171 View in Reaxys Reaction Steps: 4 1: SOCl2 / benzene 2: aq. NH3 3: Br2 / methanol 4: KOH / bis-(2-hydroxy-ethyl) ether With potassium hydroxide, ammonium hydroxide, thionyl chloride, bromine in methanol, diethylene glycol, benzene Kalir,A.; Pelah,K.; Israel Journal of Chemistry; vol. 5; (1967); p. 223 - 229 View in Reaxys Reaction Steps: 2 1: SOCl2 / dimethylformamide 2: (i) NaN3, xylene, (ii) aq. HCl With thionyl chloride in N,N-dimethyl-formamide Bonnekessel,J.; Ruechardt,C.; Chemische Berichte; vol. 106; (1973); p. 2890 - 2903 View in Reaxys

HO

H 2N

Rx-ID: 1032538 View in Reaxys 4/26 Yield

Conditions & References With potassium cyanide, sulfuric acid in anhydrous butyl ether, T= 60 - 80 °C Christol,H. et al.; Bulletin de la Societe Chimique de France; (1961); p. 2319 - 2324 View in Reaxys (i) NaN3, CF3CO2H, CHCl3, (ii) Raney-Ni, iPrOH, Multistep reaction Balderman,D.; Kalir,A.; Synthesis; (1978); p. 24 - 26 View in Reaxys Reaction Steps: 2 1: NaN3, CF3COOH / CHCl3 / 1.) 5 deg C, 2.) room temp., overnight 2: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys Reaction Steps: 2 1: sodium azide; trifluoroacetic acid / dichloromethane / 1.25 h / -5 - 0 °C / Inert atmosphere 2: lithium aluminium tetrahydride / diethyl ether / 3 h / 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in diethyl ether, dichloromethane Tagad, Harichandra D.; Hamada, Yoshio; Nguyen, Jeffrey-Tri; Hidaka, Koushi; Hamada, Takashi; Sohma, Youhei; Kimura, Tooru; Kiso, Yoshiaki; Bioorganic and Medicinal Chemistry; vol. 19; nb. 17; (2011); p. 5238 5246 View in Reaxys Reaction Steps: 2

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1: sodium azide; trifluoroacetic acid / chloroform / 0 - 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 20 °C / |Inert atmosphere With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, chloroform Sun, Shengguo; Wallach, Jason; Adejare, Adeboye; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 843 - 852 View in Reaxys

O

HN O

H 2N

Rx-ID: 1143882 View in Reaxys 5/26 Yield

Conditions & References With potassium hydroxide in diethylene glycol Kalir,A.; Pelah,K.; Israel Journal of Chemistry; vol. 5; (1967); p. 223 - 229 View in Reaxys

I

H 2N

racemate

Rx-ID: 1383884 View in Reaxys 6/26 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Heating Drefahl,G. et al.; Journal fuer Praktische Chemie (Leipzig); vol. 23; (1964); p. 136 - 142 View in Reaxys

N H 2N

N N

Rx-ID: 1971107 View in Reaxys 7/26 Yield 99 %

Conditions & References With hydrazine hydrate in ethanol, T= 20 °C , chemoselective reaction Udumula, Venkatareddy; Nazari, S. Hadi; Burt, Scott R.; Alfindee, Madher N.; Michaelis, David J.; ACS Catalysis; vol. 6; nb. 7; (2016); p. 4423 - 4427 View in Reaxys

75 %

Preparation of 1-(1-phenylcyclohexyl)amine General procedure: The azide (5.0 g, 21 mmol) was dissolved in 20 ml dryTHF and the mixture was then added dropwise over 30 minto a stirred solution of lithium aluminum hydride (LAH, 2.4g, 63 mmol) in 40 ml dry THF at 0 °C under nitrogen. Uponcompletion of the addition, the reaction was allowed to recoverto room temperature. After 12 hours, the mixture wasplaced on ice and carefully quenched with water and a fewdrops of 2N aqueous KOH solution. The slurry was dilutedwith ether and gravity filtered and the salts washed withether. Ether (100 ml) was added and the organic phase extractedwith 2N HCl solution (3 x 20 ml). The acidic fractionswere pooled and adjusted to pH 10 with ammonia solution(or alternatively KOH) followed by extraction with ether(3 x 40 ml). The ethereal extracts were pooled, dried overanhydrous sodium sulfate and reduced under vacuum to givethe crude amine as a yellow oil. This oil was purified by columnchromatography using a mixture of CHCl3 and diethylether (9:1, v/v) as mobile phase to give 1-(4-fluorophenyl)cycloheptanamine 3 With lithium aluminium tetrahydride in tetrahydrofuran, Time= 12h, T= 0 - 20 °C , Inert atmosphere Sun, Shengguo; Wallach, Jason; Adejare, Adeboye; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 843 - 852 View in Reaxys

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67 %

5.2.6. 1-Phenylcyclohexylamine (8b) General procedure: A solution of 1-phenylcyclopentylazide 7a (132 mg, 1.42 mmol) in diethyl ether (Et2O) (1 mL) was added dropwise to a suspension of lithium aluminum hydride (54 mg, 1.42 mmol) in Et2O (4 mL). The mixture was stirred at room temperature under nitrogen for 3 h, whereupon the reaction was quenched with 1 N NaOH (aq). The reaction mixture was then partitioned between Et2O (5 mL) and 1 N HCl (aq) (5 mL). The aqueous layer was collected and basified with 28percent NH4OH (aq) and extracted with CHCl3. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained crude product 8a (70.5 mg, 62percent) was used directly for next step without further purification. With lithium aluminium tetrahydride in diethyl ether, Time= 3h, T= 20 °C , Inert atmosphere Tagad, Harichandra D.; Hamada, Yoshio; Nguyen, Jeffrey-Tri; Hidaka, Koushi; Hamada, Takashi; Sohma, Youhei; Kimura, Tooru; Kiso, Yoshiaki; Bioorganic and Medicinal Chemistry; vol. 19; nb. 17; (2011); p. 5238 5246 View in Reaxys

38 %

With Raney nickel in isopropyl alcohol, T= 60 - 70 °C Balderman, David; Kalir, Asher; ; vol. 60; (1981); p. 104 View in Reaxys With lithium aluminium tetrahydride in diethyl ether, Time= 3h, Yield given Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys

H 2N

Rx-ID: 7715439 View in Reaxys 8/26 Yield

Conditions & References 1-Phenyl-cyclohexen, NaCN, Dibutylaether, H2SO4 <40grad> MADDOX; GODEFROI; PARCELL; Journal of medicinal chemistry; vol. 8; (1965); p. 230 - 235 View in Reaxys 1-Phenyl-cyclohexancarbonsaeure-amid, Br2, aq.KOH MADDOX; GODEFROI; PARCELL; Journal of medicinal chemistry; vol. 8; (1965); p. 230 - 235 View in Reaxys 1-Phenyl-cyclohexan-carbonsaeure-amid, Br2, aq. KOH; (als Hydrochlorid isoliert) MADDOX; GODEFROI; PARCELL; Journal of medicinal chemistry; vol. 8; (1965); p. 230 - 235 View in Reaxys N-Methoxycarbonyl-1-phenyl-cyclohexylamin I, ethanol. KOH Patent; Tanabe Seiyaku Co.Ltd.; JP652662; (1959); ; vol. 58; nb. 13842; (1963) View in Reaxys nach bek.Methode Brine; Williams; Boldt; Carroll; Journal of Heterocyclic Chemistry; vol. 16; nb. 7; (1979); p. 1425 - 1429 View in Reaxys entspr. Literaturzitat 7 Kalir et al.; European Journal of Medicinal Chemistry; vol. 13; (1978); p. 17,18 View in Reaxys 1-Phenylcyclohexylamin, Tritium, PdO2

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Kalir et al.; European Journal of Medicinal Chemistry; vol. 13; (1978); p. 17,18 View in Reaxys 85 Patent; PHARMACOPEIA, INC.; WO2004/33440; (2004); (A1) English View in Reaxys 85 Patent; Schering Corporation and Pharmacopeia, Inc.; US2004/147559; (2004); (A1) English View in Reaxys 5 : 1-(Bis-3,5-trifluoromethylbenzyoxy)-2-amino-2-phenylcyclohexane EXAMPLE 5 1-(Bis-3,5-trifluoromethylbenzyoxy)-2-amino-2-phenylcyclohexane The title compound was prepared using an analogous procedure as outlined in Example 1 but using Bis-3,5-trifluoromethylbenzyl alcohol. 1 H NMR (360 MHz, DMSO) δ 1.40-1.52 (2H, m), 2.61-2.73 (2H, m), 2.78-2.84 (2H, m), 1.98-2.04 (1H, m), 2.06-2.09 (1H, m), 4.02 (1H, t, J=6.3 Hz), 4.50, 4.79 (2H, ABq, J=12.9 Hz), 7.33-7.43 (3H, m), 7.59-7.61 (2H, m), 7.85 (2H, s) and 7.96 (1H, s). The oxalate salt was recrystallized from ethanol/water mp 119°-122° C. Found: C, 53.96; H, 4.48; N, 2.70; C21 H21 F6 NO.C2 H2 O4.(0.25)H2 O; C, 53.96; H, 4.62; N, 2.73percent. Patent; Merck Sharp and Dohme Limited; US5627211; (1997); (A1) English View in Reaxys O

H 2N

Rx-ID: 21931900 View in Reaxys 9/26 Yield

Conditions & References Reaction Steps: 3 1: tetrahydrofuran / 0.33 h 2: NaN3, CF3COOH / CHCl3 / 1.) 5 deg C, 2.) room temp., overnight 3: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys Reaction Steps: 3 1.1: magnesium / tetrahydrofuran / 1.17 h / Cooling with ice; Reflux 1.2: 3 h / 0 - 20 °C 2.1: sodium azide; trifluoroacetic acid / dichloromethane / 1.25 h / -5 - 0 °C / Inert atmosphere 3.1: lithium aluminium tetrahydride / diethyl ether / 3 h / 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, magnesium, trifluoroacetic acid in tetrahydrofuran, diethyl ether, dichloromethane, 1.2: Grignard reaction / 1.3: Grignard reaction Tagad, Harichandra D.; Hamada, Yoshio; Nguyen, Jeffrey-Tri; Hidaka, Koushi; Hamada, Takashi; Sohma, Youhei; Kimura, Tooru; Kiso, Yoshiaki; Bioorganic and Medicinal Chemistry; vol. 19; nb. 17; (2011); p. 5238 5246 View in Reaxys

Br–+Mg

H 2N

Rx-ID: 21932867 View in Reaxys 10/26 Yield

Conditions & References Reaction Steps: 3

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1: tetrahydrofuran / 0.33 h 2: NaN3, CF3COOH / CHCl3 / 1.) 5 deg C, 2.) room temp., overnight 3: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys

H 2N

Rx-ID: 22125803 View in Reaxys 11/26 Yield

Conditions & References Reaction Steps: 2 1: nitric acid / 100 - 110 °C / im geschlossenen Rohr 2: tin; hydrochloric acid With hydrogenchloride, tin, nitric acid Kurssanow; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 38; (1906); p. 1300; Chem. Zentralbl.; vol. 78; nb. I; (1907); p. 1744 View in Reaxys

H 2N

N

Rx-ID: 22429836 View in Reaxys 12/26 Yield

Conditions & References Reaction Steps: 3 1: aq. KOH / ethane-1,2-diol / Heating 2: SOCl2 / Heating 3: (i) NaN3, toluene, (ii) aq. HCl, toluene With potassium hydroxide, thionyl chloride in ethylene glycol Carissimi; D'Ambrosio; Grumelli; Milla; Ravenna; Il Farmaco; edizione scientifica; vol. 21; nb. 2; (1966); p. 155 171 View in Reaxys Reaction Steps: 5 1: KOH / bis-(2-hydroxy-ethyl) ether 2: SOCl2 / benzene 3: aq. NH3 4: Br2 / methanol 5: KOH / bis-(2-hydroxy-ethyl) ether With potassium hydroxide, ammonium hydroxide, thionyl chloride, bromine in methanol, diethylene glycol, benzene Kalir,A.; Pelah,K.; Israel Journal of Chemistry; vol. 5; (1967); p. 223 - 229 View in Reaxys Reaction Steps: 3 1: KOH / bis-(2-hydroxy-ethyl) ether 2: SOCl2 / dimethylformamide 3: (i) NaN3, xylene, (ii) aq. HCl With potassium hydroxide, thionyl chloride in N,N-dimethyl-formamide, diethylene glycol Bonnekessel,J.; Ruechardt,C.; Chemische Berichte; vol. 106; (1973); p. 2890 - 2903 View in Reaxys

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H 2N

Rx-ID: 22430997 View in Reaxys 13/26 Yield

Conditions & References Reaction Steps: 2 1: (i) silver fulminate, I2, Et2O, (ii) aq. HCl 2: LiAlH4 / tetrahydrofuran / Heating With lithium aluminium tetrahydride in tetrahydrofuran Drefahl,G. et al.; Journal fuer Praktische Chemie (Leipzig); vol. 23; (1964); p. 136 - 142 View in Reaxys

H 2N

O

Rx-ID: 22441418 View in Reaxys 14/26 Yield

Conditions & References Reaction Steps: 2 1: Br2 / methanol 2: KOH / bis-(2-hydroxy-ethyl) ether With potassium hydroxide, bromine in methanol, diethylene glycol Kalir,A.; Pelah,K.; Israel Journal of Chemistry; vol. 5; (1967); p. 223 - 229 View in Reaxys

n-butyl halide

N

H 2N

Rx-ID: 22749755 View in Reaxys 15/26 Yield

Conditions & References Reaction Steps: 4 1: KOtBu / 2-methyl-propan-2-ol 2: KOH / bis-(2-hydroxy-ethyl) ether 3: SOCl2 / dimethylformamide 4: (i) NaN3, xylene, (ii) aq. HCl With potassium hydroxide, thionyl chloride, potassium tert-butylate in N,N-dimethyl-formamide, tert-butyl alcohol, diethylene glycol Bonnekessel,J.; Ruechardt,C.; Chemische Berichte; vol. 106; (1973); p. 2890 - 2903 View in Reaxys

etherol

H

N

O

H

H 2N

N N

Rx-ID: 24426157 View in Reaxys 16/26 Yield

Conditions & References 88 : 1-Phenylcyclohexylamine The crude azide (18.0 g, <=96 mmol) was dissolved in dioxane (300 mL) with triphenylphosphine (40 g, 152 mmol) and the stirred solution was refluxed for 4 h. under N2 (g) before adding H2 O (9 mL, 0.5 mol). After about 46 h. further reflux, solvent was removed in vacuo at about 45-50° C. and residual moisture was removed by azeotropic distillations in vacuo with CH3 CN and Et2 O, respectively. The syrupy residue was dissolved in boiling Et2 O and chilled to about 0° C. for about 16 h.

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Precipitated Ph3 PO was removed by filtration, and 1M HCl in Et2 O (90 mL) was added dropwise at about 5° C. to the etherol filtrate to precipitate the desired 1-phenyl-cyclohexylamine as its HCl salt (12.7 g, LC-MS m/z 162 (MH+)) which was recrystallized from CHCl3 /i-Pr2 O before use. With hydrogenchloride, triphenylphosphine in 1,4-dioxane, diethyl ether, acetonitrile Patent; Pfizer Inc; US6130217; (2000); (A1) English View in Reaxys

O N H

O

H 2N

Rx-ID: 24813277 View in Reaxys 17/26 Yield

Conditions & References

90 %

28 :Preparation 28; 1 -Phenyl-cyclohexylamine; Dissolve (l-phenyl-cyclohexyl)-carbamic acid benzyl ester (Preparation 27) (2.87 g, 9.26 mmol) in MeOH (100 mL). Exchange air with nitrogen for three times and then EPO <DP n="64"/>add Pd-C (0.5 g, 10percent). Exchange the nitrogen with H2 for three times. Stir the reaction mixture under H2 for over night then remove the Pd-C by filtration. Remove the solvent under reduced pressure to give 1.468 g (90percent) of the crude title compound as a colorless oil. With hydrogen, palladium 10 on activated carbon in methanol Patent; ELI LILLY AND COMPANY; WO2006/49952; (2006); (A1) English View in Reaxys

I H 2N

Rx-ID: 31541049 View in Reaxys 18/26 Yield

Conditions & References Reaction Steps: 3 1.1: magnesium / tetrahydrofuran / 1.17 h / Cooling with ice; Reflux 1.2: 3 h / 0 - 20 °C 2.1: sodium azide; trifluoroacetic acid / dichloromethane / 1.25 h / -5 - 0 °C / Inert atmosphere 3.1: lithium aluminium tetrahydride / diethyl ether / 3 h / 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, magnesium, trifluoroacetic acid in tetrahydrofuran, diethyl ether, dichloromethane, 1.2: Grignard reaction / 1.3: Grignard reaction Tagad, Harichandra D.; Hamada, Yoshio; Nguyen, Jeffrey-Tri; Hidaka, Koushi; Hamada, Takashi; Sohma, Youhei; Kimura, Tooru; Kiso, Yoshiaki; Bioorganic and Medicinal Chemistry; vol. 19; nb. 17; (2011); p. 5238 5246 View in Reaxys

F

H N

F O

H 2N

Rx-ID: 35902160 View in Reaxys 19/26 Yield 91 %

Conditions & References With sodium hydroxide in methanol, Time= 7h, Reflux Miyoshi, Tetsuya; Matsuya, Syota; Tsugawa, Mikako; Sato, Shohei; Ueda, Masafumi; Miyata, Okiko; Organic Letters; vol. 15; nb. 13; (2013); p. 3374 - 3377 View in Reaxys

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O

N

HN

H 2N

O

OH

Rx-ID: 4345960 View in Reaxys 20/26 Yield

Conditions & References With sodium dithionite, potassium carbonate, N,N'-dioctyl-4,4'-bipyridinium in water, acetonitrile, Time= 2h, T= 35 °C , Yield given. Yields of byproduct given Park, Kwanghee Koh; Oh, Chang Hun; Sim, Woo-Jeon; Journal of Organic Chemistry; vol. 60; nb. 19; (1995); p. 6202 - 6204 View in Reaxys

N H

Cl

H

Cl

H

H 2N

Rx-ID: 3620921 View in Reaxys 21/26 Yield

Conditions & References With hydrogenchloride, hydrogen, palladium on activated charcoal in ethanol, Time= 24h, T= 50 °C , p= 2585.7Torr , Yield given Baker; Little; Journal of Medicinal Chemistry; vol. 28; nb. 1; (1985); p. 46 - 50 View in Reaxys

Br N

Mg

Br Cl

H

H 2N

Rx-ID: 29350182 View in Reaxys 22/26 Yield

Conditions & References

13 %

Stage 1: in diethyl ether, Time= 0.5h, T= 20 °C Stage 2: With titanium (IV) isopropoxide in diethyl ether, Time= 24h, T= 20 °C , Further stages Tomashenko, Olesya A.; Rudenko, Andrei E.; Sokolov, Viktor V.; Tomashevskiy, Alexander A.; De Meijere, Armin; European Journal of Organic Chemistry; nb. 8; (2010); p. 1574 - 1578 View in Reaxys

Cl H 2N

H

H 2N

Rx-ID: 40018320 View in Reaxys 23/26 Yield

Conditions & References General procedure: The HCl salt 4 was obtained by bubbling HCl gas into anethereal solution of the free base With hydrogenchloride in diethyl ether Sun, Shengguo; Wallach, Jason; Adejare, Adeboye; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 843 - 852 View in Reaxys

Cl HO

H

H 2N

Rx-ID: 40018347 View in Reaxys 24/26 Yield

Conditions & References Reaction Steps: 3

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1: sodium azide; trifluoroacetic acid / chloroform / 0 - 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 20 °C / |Inert atmosphere 3: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, diethyl ether, chloroform Sun, Shengguo; Wallach, Jason; Adejare, Adeboye; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 843 - 852 View in Reaxys

Cl

N

H

H 2N

N N

Rx-ID: 40018348 View in Reaxys 25/26 Yield

Conditions & References Reaction Steps: 2 1: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 20 °C / |Inert atmosphere 2: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether Sun, Shengguo; Wallach, Jason; Adejare, Adeboye; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 843 - 852 View in Reaxys

Cl H 2N

O

H

H 2N

Rx-ID: 45682031 View in Reaxys 26/26 Yield 47.2 %

Conditions & References 6.3 : Synthesis of 1-phenylcyclohexane-1-amine hydrochloride In step 2 manufactured 1-phenylcyclohexane-1-carboxamide (1.090 g, 5.362 mmol) and sodium hydroxide (3.00 M solution in water, 5.004 mL, 15.013 mmol) Was dissolved in 1-butanol (30 mL) was stirred at 0 °C for 1 hour, and sodium hypochlorite (11.00percent, 5.080 g, 7.507 mmol), and the mixture was further stirred at room temperature for 17 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was dissolved in ethyl acetate, and hydrochloric acid (4 M solution, 2.011 mL, 8.043 mmol) was added and stirred. The precipitated solid was filtered, washed with ethyl acetate and dried to give the title compound (0.536 g, 47.2percent) as a white solid. Stage 1: With sodium hydroxide in water, butan-1-ol, Time= 1h, T= 0 °C , Hofmann Rearrangement Stage 2: With sodium hypochlorite in water, butan-1-ol, Time= 17h, T= 20 °C Stage 3: With hydrogenchloride in ethyl acetate Patent; Chong Kun Dang Co., Ltd.; Kim, Yoon Tae; Lee, Chang Sik; Oh, Jung Taek; Song, Hey Sung; Choe, Jin; Lee, Jae Young; (210 pag.); KR2017/43091; (2017); (A) Korean View in Reaxys

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