Lithium Hydroxide → HCID 59249437, compound

HRID 1807220Notes

Reaction equation

HRID 1807220 reaction equation
C[O:2][C:3]([C:5]1([NH:8][C:9]([C@H:11]2[C@H:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=3[F:23])[C@:14]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:13]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[NH:12]2)=[O:10])[CH2:7][CH2:6]1)=[O:4].[Li+].[OH-]>C1COCC1.CO.O.C(OCC)(=O)C>[Cl:22][C:18]1[C:17]([F:23])=[C:16]([C@@H:15]2[C@:14]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:13]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[NH:12][C@H:11]2[C:9]([NH:8][C:5]2([C:3]([OH:4])=[O:2])[CH2:6][CH2:7]2)=[O:10])[CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 2

HCID 3939Lithium HydroxideHCID 68617646Rac-1-{[(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}-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 59249437HCID 59249437, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The ester was taken directly to the hydrolysis step by dissolved in THF (3 mL) and methanol (1 mL), then 2N LiOH (1 mL) was added and stirred at room temperature for 3 hours. The mixture was diluted with water and ethyl acetate, the organic phase was separated then concentrated under reduced pressure to rac-1-{[(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}-cyclopropanecarboxylic acid (65.2 mg, 67.2%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H27Cl2F2N3O3+H [(M+H)+]: 550.1471. found: 550.1471.

Workup

  1. customthe organic phase was separated
  2. concentrationthen concentrated under reduced pressure to rac-1-{[(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}-cyclopropanecarboxylic acid (65.2 mg, 67.2%) as an off-white powder

Sources & evidence

ORD record
ord-6b461dd3036843b8882882b34be987a6
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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