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

HRID 1806933ノート

反応式

HRID 1806933 の反応式
[C:1]([O:5][C:6](=[O:23])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH3:22])([CH3:21])[CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[C:26]([F:43])=[C:27](/[CH:31]=[C:32](/[C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=2[F:42])\[C:33]#[N:34])[CH:28]=[CH:29][CH:30]=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:31]([C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([Cl:24])[C:26]=2[F:43])[C:32]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=2[F:42])([C:33]#[N:34])[CH:9]([CH2:10][C:11]([CH3:22])([CH3:21])[CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[NH:8]1)=[O:23])([CH3:3])([CH3:2])[CH3:4]

参加物

7

反応物 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 178446421HCID 178446421、化合物

生成物 1

HCID 66666380rac-(2R,3S,4R,5S)-5-[3-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester収率 61.2%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 6386tert-Butanol溶媒

実験手順

In a manner similar to the method described in Example 100b, [4-(tert-butyl-dimethyl-silanyloxy)-3,3-dimethyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 105a (1.25 g, 3.64 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (0.93 g, 3 mmol) prepared in Example 52a, AgF (0.57 g, 4.5 mmol), and triethylamine (1.05 mL, 7.5 mmol) in dichloromethane (100 mL) at room temperature for 18 h, followed by the reaction with DBU (3.6 ml) in tert-butanol (15 mL) at 100° C. for 2 h to give rac-(2R,3S,4R,5S)-5-[3-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-propyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a white solid (1.2 g, 61%).

出典と根拠

ORDレコード
ord-ee7a16e3a9c44ed690c5cfead2497d4b
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

読み込み中…