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Triethylamine → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[2-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-propyl]-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1807050
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HRID 1807050 반응식
[C:1]([O:5][C:6](=[O:20])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([C:14]1[CH2:15][CH2:16][O:17][CH2:18][CH:19]=1)([CH3:13])[CH3:12])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[C:23]([F:40])=[C:24](/[CH:28]=[C:29](/[C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=2[F:39])\[C:30]#[N:31])[CH:25]=[CH:26][CH:27]=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:28]([C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([Cl:21])[C:23]=2[F:40])[C:29]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=2[F:39])([C:30]#[N:31])[CH:9]([CH2:10][C:11]([C:14]2[CH2:19][CH2:18][O:17][CH2:16][CH:15]=2)([CH3:13])[CH3:12])[NH:8]1)=[O:20])([CH3:2])([CH3:3])[CH3:4]
참가 물질실험 절차출처 및 근거반응 노트

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 178451253HCID 178451253, 화합물

생성물 1

HCID 67297242rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[2-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-propyl]-pyrrolidine-2-carboxylic acid tert-butyl ester
수율 75%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6386tert-Butanol용매

실험 절차

In a manner similar to the method described in Example 100b, [3-(3,6-dihydro-2H-pyran-4-yl)-3-methyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 129a (4.3 g, 15.5 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (3.8 g, 12.4 mmol) prepared in Example 52a, AgF (2.4 g, 19 mmol), and triethylamine (4.3 mL, 31 mmol) in dichloromethane (100 mL) at room temperature for 18 h, followed by the reaction with DBU (19 ml) in tert-butanol (18 mL) at 100° C. for 2 h to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[2-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-propyl]-pyrrolidine-2-carboxylic acid tert-butyl ester as a yellow gum (5.5 g, 75%).

출처 및 근거

ORD 기록
ord-b8be0e047b0e45e7bfcead57978bb5da
출처 데이터셋
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08354444B2

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