Triethylamine → rac-(2R,3S,4R,5S)-5-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-2,2-dimethyl-butyl}-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1807001노트

반응식

HRID 1807001 반응식
[C:1]([O:5][C:6](=[O:27])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH3:26])([CH3:25])[CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])([CH3:4])([CH3:3])[CH3:2].[Cl:28][C:29]1[C:30]([F:47])=[C:31](/[CH:35]=[C:36](/[C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[F:46])\[C:37]#[N:38])[CH:32]=[CH:33][CH:34]=1.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1>ClCCl.C(O)(C)(C)C>[C:1]([O:5][C:6]([CH:7]1[CH:35]([C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([Cl:28])[C:30]=2[F:47])[C:36]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[F:46])([C:37]#[N:38])[CH:9]([CH2:10][C:11]([CH3:26])([CH3:25])[CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[NH:8]1)=[O:27])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59249629(Z)-3-(3-Chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrileHCID 178446420HCID 178446420, 화합물

생성물 1

HCID 67296795rac-(2R,3S,4R,5S)-5-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-2,2-dimethyl-butyl}-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester수율 68.8%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6386tert-Butanol용매

실험 절차

In a manner similar to the method described in Example 100b, [5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,3-dimethyl-pent-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 119a (0.4 g, 1 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (0.3 g, 1 mmol) prepared in Example 52a, AgF (0.2 g, 1.5 mmol), and triethylamine (0.3 mL, 2.4 mmol) in dichloromethane (50 mL) at room temperature for 18 h, followed by the reaction with DBU (1 ml) in tert-butanol (2 mL) at 100° C. for 2 h to give rac-(2R,3S,4R,5S)-5-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-2,2-dimethyl-butyl}-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a white gum (0.49 g, 60%).

출처 및 근거

ORD 기록
ord-5f42b669db4e44a8b0ea36eb70049de2
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354444B2

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