Lithium Hydroxide → HCID 51356121, compound

HRID 909067Notes

Reaction equation

HRID 909067 reaction equation
C([O:3][C:4](=[O:34])[CH2:5][N:6]1[CH2:10][C@@H:9]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C@@:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[F:25])([C:16]#[N:17])[C@H:7]1[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=1[F:33])C.[Li+].[OH-]>C1COCC1.O>[Cl:32][C:28]1[C:27]([F:33])=[C:26]([C@@H:7]2[C@:8]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[F:25])([C:16]#[N:17])[C@H:9]([CH2:11][C:12]([CH3:14])([CH3:15])[CH3:13])[CH2:10][N:6]2[CH2:5][C:4]([OH:34])=[O:3])[CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 51356118HCID 51356118, compound

Product 1

HCID 51356121HCID 51356121, compoundYield 102.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of rac [(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid ethyl ester (14.7 mg, 0.0288 mmol, Example C1) in THF (1.8 mL) was added a solution of LiOH (Aldrich, 8.5 mg, 0.02 mmol) in water (1.2 mL) and the reaction mixture was stirred at rt for 22 hrs. The reaction mixture was partly concentrated and quenched with 1 N HCl (pH 4-5), extracted with EtOAc, and washed with water, saturated NaCl. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated to give rac-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid (14.2 mg, 102%). HRMS (ES+) m/z Calcd for C24H24Cl2F2N2O2+H [(M+H)+]: 481.1256; Found: 481.1255.

Workup

  1. concentrationThe reaction mixture was partly concentrated
  2. customquenched with 1 N HCl (pH 4-5)
  3. extractionextracted with EtOAc
  4. washwashed with water, saturated NaCl
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was then concentrated

Sources & evidence

ORD record
ord-06b3fd0b4fe7454ab3b29ab507b6bf5d
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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