Potassium Hydroxide → 5-{[(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}-1H-indole-2-carboxylic acid

HRID 1807256Notes

Reaction equation

HRID 1807256 reaction equation
C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([NH:15][C:16]([C@H:18]1[C@H:22]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=3[F:30])[C@:21]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=3[F:40])([C:31]#[N:32])[C@H:20]([CH2:41][C:42]([CH3:45])([CH3:44])[CH3:43])[NH:19]1)=[O:17])=[CH:10][CH:9]=2)=[O:5])C.[OH-].[K+]>C(O)C.O>[Cl:29][C:25]1[C:24]([F:30])=[C:23]([C@@H:22]2[C@:21]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=3[F:40])([C:31]#[N:32])[C@H:20]([CH2:41][C:42]([CH3:44])([CH3:45])[CH3:43])[NH:19][C@H:18]2[C:16]([NH:15][C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:14]3)=[O:17])[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 592493995-{[(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}-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 592495895-{[(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}-1H-indole-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A chiral 5-{[(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}-1H-indole-2-carboxylic acid ethyl ester (33 mg, 0.051 mmol) was dissolved in ethanol (15 mL), then 2N KOH (5 mL) was added and stirred 2 hours @ 50° C., then the temperature was warmed to 65° C. for 2 h, after cooling to 25° C., the reaction was diluted with water and extracted with ethyl acetate (3×). The organic phase was separated then concentrated under reduce pressure to chiral 5-{[(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}-1H-indole-2-carboxylic acid (24 mg, 76%) as a white powder. HRMS (ES+) m/z Calcd for C32H28Cl2F2N4O3+H [(M+H)+]: 625.1580 found: 625.1580.

Workup

  1. temperaturethe temperature was warmed to 65° C. for 2 h
  2. temperatureafter cooling to 25° C.
  3. extractionextracted with ethyl acetate (3×)
  4. customThe organic phase was separated
  5. concentrationthen concentrated

Sources & evidence

ORD record
ord-0c4ac85d0b79447cb168a91cdebc69c5
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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