Hydrochloric Acid → 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid

HRID 403361Notes

Reaction equation

HRID 403361 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:29])[CH2:18][N:19]3[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[N:20]3)[CH2:13][CH2:12]2)[S:9][CH:10]=1)=[O:5])C.[OH-].[Na+].Cl>C1COCC1>[CH3:24][C:23]1[N:19]([CH2:18][C:17]([N:14]2[CH2:15][CH2:16][CH:11]([C:8]3[S:9][CH:10]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=3)[CH2:12][CH2:13]2)=[O:29])[N:20]=[C:21]([C:25]([F:28])([F:26])[F:27])[CH:22]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66911511ethyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate

Product 1

HCID 666014572-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl ester (2.67 g, 6.2 mmol) in THF (20 mL) is added aqueous solution of sodium hydroxide (2 M, 4.65 mL, 9.3 mmol) at RT. After stirring 3 h at RT, the reaction mixture is acidified with 2M aqueous solution of HCl until pH 2-3, and the solution is extracted with ethylacetate (20 mL). The aqueous layer is re-extracted with ethylacetate (20 mL) and the combined organic layers are washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure to give 2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid (2.33 g, 94%), which can be used in the next step without further purification. 1H-NMR (400 MHz, d6-acetone): δ=1.69-1.82 (m, 1H), 1.87-2.02 (m, 1H), 2.16-2.37 (m, 2H), 2.38 (s, 3H), 2.89-2.99 (m, 1H), 3.38-3.48 (m, 2H), 4.14-4.22 (m, 1H), 4.50-4.69 (m, 1H), 5.20-5.36 (2 d, 2H (diastereotopic)), 6.41, (s, 1H), 8.34 (s, 1H). MS: m/z=403 (M+1).

Workup

  1. extractionthe solution is extracted with ethylacetate (20 mL)
  2. extractionThe aqueous layer is re-extracted with ethylacetate (20 mL)
  3. washthe combined organic layers are washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-adaa526f1ec64b75a2d003b9b6aab69a
Source dataset
uspto-grants-2014_06
Patent number
US08748431B2

Reaction notes

Loading…