Lithium Hydroxide → HCID 53357224, compound

HRID 1807259Notes

Reaction equation

HRID 1807259 reaction equation
C[O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH:8]([CH2:11][NH:12][C:13]([C@H:15]2[C@H:19]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=3[F:27])[C@:18]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=3[F:37])([C:28]#[N:29])[C@H:17]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:16]2)=[O:14])[CH2:7][CH2:6]1)=[O:4].[Li+].[OH-]>C1COCC1.O>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([C@@:18]2([C:28]#[N:29])[C@H:17]([CH2:38][C:39]([CH3:42])([CH3:40])[CH3:41])[NH:16][C@@H:15]([C:13]([NH:12][CH2:11][CH:8]3[CH2:7][CH2:6][CH:5]([C:3]([OH:4])=[O:2])[CH2:10][CH2:9]3)=[O:14])[C@@H:19]2[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=2[F:27])=[C:31]([F:37])[CH:32]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 53358940HCID 53358940, compound

Product 1

HCID 53357224HCID 53357224, compoundYield 98.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac 4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-cyclohexanecarboxylic acid methyl ester (54.3 mg, 0.0875 mmol, example XC-1) in THF (5 mL) was added a solution of LiOH (27.8 mg, 0.662 mmol, Aldrich) in water (2.5 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 6), 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-4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-cyclohexanecarboxylic acid (52.1 mg, 98%). HRMS (ES+) m/z Calcd C31H35Cl2F2N3O3+H [(M+H): 606.2097. Found: 606.2097.

Workup

  1. concentrationThe reaction mixture was partly concentrated
  2. customquenched with 1 N HCl (pH 6)
  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-42dc4e52fda548378b0628d8e1373c80
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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