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Lithium Hydroxide → (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid

HRID 1807239
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HRID 1807239 반응식
C[O:2][C:3](=[O:42])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C@H:14]2[C@H:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[F:26])[C@:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:15]2)=[O:13])=[CH:7][CH:6]=1.[Li+].[OH-]>C1COCC1.CO>[Cl:25][C:21]1[C:20]([F:26])=[C:19]([C@@H:18]2[C@:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:15][C@H:14]2[C:12]([NH:11][C:8]2[CH:7]=[CH:6][C:5]([CH2:4][C:3]([OH:42])=[O:2])=[CH:10][CH:9]=2)=[O:13])[CH:24]=[CH:23][CH:22]=1
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참가 물질

5

반응물 2

HCID 3939Lithium HydroxideHCID 59249533(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid methyl ester

생성물 1

HCID 59249266(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid수율 52.7%

시약·촉매·용매 2

HCID 887
Methanol
용매
HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid methyl ester (72 mg, 0.117 mmol) was dissolved in THF (3 mL) and methanol (1 mL), then 2N LiOH (1 mL) was added and stirred at room temperature for 2 hours. The mixture was concentrated and diluted with water and ethyl acetate. The organic phase was separated then concentrated to yield chiral (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid (37 mg, 52.6%) as an white powder. HRMS (ES+) m/z Calcd for C31H29Cl2F2N3O3+H [(M+H)+]: 600.1627. found: 600.1626.

후처리

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water and ethyl acetate
  3. customThe organic phase was separated
  4. concentrationthen concentrated

출처 및 근거

ORD 기록
ord-6a86b3dc948a4b5daca99f3d1bd81085
출처 데이터셋
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08354444B2

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