Lithium Hydroxide → HCID 178444597, compound

HRID 1807205Notes

Reaction equation

HRID 1807205 reaction equation
C[O:2][C:3](=[O:41])[CH2:4][C:5]1[NH:9][C:8]([NH:10][C:11]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=3[F:25])[C@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=3[F:35])([C:26]#[N:27])[C@H:15]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[NH:14]2)=[O:12])=[N:7][N:6]=1.[Li+].[OH-]>C1COCC1.CO>[Cl:24][C:20]1[C:19]([F:25])=[C:18]([C@@H:17]2[C@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=3[F:35])([C:26]#[N:27])[C@H:15]([CH2:36][C:37]([CH3:39])([CH3:40])[CH3:38])[NH:14][C@H:13]2[C:11]([NH:10][C:8]2[NH:9][C:5]([CH2:4][C:3]([OH:41])=[O:2])=[N:6][N:7]=2)=[O:12])[CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 178499645HCID 178499645, compound

Product 1

HCID 178444597HCID 178444597, compoundYield 34.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of rac-(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}-4H-[1,2,4]triazol-3-yl)-acetic acid methyl ester (20 mg, 0.033 mmol) was dissolved in THF (0.6 mL) and methanol (0.2 mL), then 2N LiOH (0.2 mL) was added and stirred at room temperature for 3 hours. The mixture was concentrated and diluted with water and ethyl acetate. The organic phase was separated then concentrated to yield rac-(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}-4H-[1,2,4]triazol-3-yl)-acetic acid (6.7 mg, 34%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H26Cl2F2N6O3+H [(M+H)+]: 591.1485. found: 591.1483.

Workup

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

Sources & evidence

ORD record
ord-85e2a3322f7f41d5b3c5d7890d57049c
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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