Lithium Hydroxide → (S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

HRID 408002Notes

Reaction equation

HRID 408002 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([O:23][C:24]4[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Li+].[OH-]>C1COCC1>[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([O:23][C:24]4[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 54670990(S)-methyl 4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoate

Product 1

HCID 67469817(S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acidYield 42.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-methyl 4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoate (0.1 g, 0.19 mmol) in THF (2 mL) was added LiOH (3 M, 2 mL) and the reaction was stirred overnight at ambient temperature. The THF was removed with a stream of nitrogen. The aqueous layer was acidified with 1 N HCl to about pH 1 and the solid that formed was filtered and washed with water. The solid was dried under vacuum to yield (S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (0.040 g, 0.081 mmol, 42% yield).

Workup

  1. customThe THF was removed with a stream of nitrogen
  2. customthe solid that formed
  3. filtrationwas filtered
  4. washwashed with water
  5. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-40cbf55b5e1146cb8b20004767be5aa0
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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