Potassium Hydroxide → rac-(2S,3S,4S)-2-(3-chloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

HRID 909010노트

반응식

HRID 909010 반응식
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:8]=[N:9]/[CH3:10])[CH:5]=[CH:6][CH:7]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](=[CH:21]/[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])/[C:19]#[N:20])=[C:14]([F:27])[CH:13]=1.[OH-].[K+]>CS(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:18]([C:15]3[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=3[F:27])([C:19]#[N:20])[CH:21]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 14797Potassium HydroxideHCID 58222872(Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrileHCID 178482757HCID 178482757, 화합물

생성물 1

HCID 67095616rac-(2S,3S,4S)-2-(3-chloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile수율 36.1%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

실험 절차

To a solution of [1-(3-chloro-phenyl)-meth-(E)-ylidene]-methyl-amine (0.77 g, 5.00 mmol) and (Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrile (1.72 g, 5.00 mmol) in DMSO (5 mL) was added KOH powder (0.56 g, 10.00 mmol) in one portion. The mixture was stirred at rt overnight. The reaction mixture was diluted with water and extracted with EtOAc three times (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, and concentrated. The residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes) after concentration to give rac-(2S,3S,4S)-2-(3-chloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (0.73 g, 36.1%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1292, rac-(2S,3S,4R)-4-(4-chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-3-(2,2-dimethyl-propyl)-pyrrolidine (0.0.42 g, 20.8%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1294, and (2S,3R,4R)-4-(4-chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-3-(2,2-dimethyl-propyl)-pyrrolidine (0.42 g, 20.8%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1294.

후처리

  1. extractionextracted with EtOAc three times (3×50 mL)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes)
  6. concentrationafter concentration

출처 및 근거

ORD 기록
ord-f9575774c88b4ca69df0166e271fdb1a
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017607B2

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