Lithium hydroxide, monohydrate → 6-(4-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)pyridine-2-carboxylic acid

HRID 1910986Notes

Reaction equation

HRID 1910986 reaction equation
[F:1][CH:2]([F:31])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[N:25]=[C:24]([C:26]([O:28]CC)=[O:27])[CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1.O.[OH-].[Li+]>O1CCCC1.O>[F:31][CH:2]([F:1])[C:3]1[CH:7]=[C:6]([CH:8]([F:9])[F:10])[N:5]([CH2:11][C:12]([N:14]2[CH2:15][CH2:16][N:17]([C:20]3[N:25]=[C:24]([C:26]([OH:28])=[O:27])[CH:23]=[CH:22][CH:21]=3)[CH2:18][CH2:19]2)=[O:13])[N:4]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66687274ethyl 6-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)pyridine-2-carboxylate

Product 1

HCID 666867066-(4-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 6-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)pyridine-2-carboxylate (1.3 g) in tetrahydrofuran (20 ml) and water (5 ml) is added, at room temperature, lithium hydroxide monohydrate (185 mg). The mixture is stirred at room temperature for 5 hours, and then ice-cold 1N HCl solution is added. The aqueous phase is extracted with ethyl acetate and then the combined organic phases are dried over sodium sulphate. The solids are filtered off and the solvent is distilled off. This gives 6-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-1-yl)pyridine-2-carboxylic acid (700 mg).

Workup

  1. extractionThe aqueous phase is extracted with ethyl acetate
  2. dry with materialthe combined organic phases are dried over sodium sulphate
  3. filtrationThe solids are filtered off
  4. distillationthe solvent is distilled off

Sources & evidence

ORD record
ord-d5ee5222ed654c61bab869c2c6347a03
Source dataset
uspto-grants-2013_12
Patent number
US08604040B2

Reaction notes

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