Lithium Hydroxide → HCID 51355011, compound

HRID 909038Notes

Reaction equation

HRID 909038 reaction equation
C([O:3][C:4](=[O:45])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([N:14]2[CH2:18][C@@H:17]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C@@:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[F:41])=[O:13])=[CH:7][C:6]=1[O:42][CH2:43][CH3:44])C.[Li+].[OH-]>C1COCC1.CO>[Cl:40][C:36]1[C:35]([F:41])=[C:34]([C@@H:15]2[C@:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:17]([CH2:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:18][N:14]2[C:12](=[O:13])[CH2:11][C:8]2[CH:9]=[CH:10][C:5]([C:4]([OH:45])=[O:3])=[C:6]([O:42][CH2:43][CH3:44])[CH:7]=2)[CH:39]=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67095469HCID 67095469, compound

Product 1

HCID 51355011HCID 51355011, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a mixture of rac-4-{2-[(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]-2-oxo-ethyl}-2-ethoxy-benzoic acid ethyl ester (50.0 mg, 0.076 mmol) in THF/MeOH (1.2 mL/0.4 mL) was added 4 N LiOH (0.4 mL), and the reaction mixture was stirred at rt for 2 hrs. The reaction mixture was concentrated and quenched with 2 NH2SO4, extracted with EtOAc, and washed with water, brine. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated and the residue was purified by RP-HPLC to give rac-4-{2-[(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]-2-oxo-ethyl}-2-ethoxy-benzoic acid (24.4 mg, 50.9%). HRMS (ES+) m/z Calcd for C33H32Cl2F2N2O4+H [(M+H)+]: 629.1780, found: 629.1782.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customquenched with 2 NH2SO4
  3. extractionextracted with EtOAc
  4. washwashed with water, brine
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was then concentrated
  8. customthe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-7dc35bc445174731ae2f932aabe6c979
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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