Lithium Hydroxide → 4-(2-Methylpiperidin-1-YL)-3-(trifluoromethyl)benzoic acid

HRID 219786Notes

Reaction equation

HRID 219786 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[CH:10][C:9]=1[C:18]([F:21])([F:20])[F:19].[OH-].[Li+]>C1COCC1.O>[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[C:18]([F:20])([F:19])[F:21]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59606551Methyl 4-(2-methylpiperidin-1-yl)-3-(trifluoromethyl)benzoate

Product 1

HCID 594956554-(2-Methylpiperidin-1-YL)-3-(trifluoromethyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-(2-methylpiperidin-1-yl)-3-(trifluoromethyl)benzoate obtained in step 2 (6.6 g, 21.9 mmol) in THF (50 mL) and water (5 mL) was added lithium hydroxide (1.84 g, 43.8 mmol). The resulting mixture was stirred at RT for 12 h. Solvents were removed under vacuum and the resulting mass was diluted with water. The aqueous layer was washed with DCM (2×50 mL) and was acidified with conc HCl (pH=4). It was extracted with EtOAc (2×100 mL). The EtOAc layer was washed with brine and dried over sodium sulfate, affording the title compound as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 13.30 (bs, 1H), 8.15-8.19 (m, 2H), 7.67-7.70 (d, 1H), 3.08 (m, 1H), 2.86-2.89 (m, 1H), 2.49-2.50 (m, 1H), 1.89-1.90 (m, 2H), 1.74-1.76 (m, 2H), 1.43-1.46 (m, 1H), 1.40-1.41 (m, 1H), 0.77 (d, 3H). LC/MS (Method A): 288.1 (M+H)+. HPLC (Method B) Rt 3.71 min (Purity: 98.3%).

Workup

  1. customSolvents were removed under vacuum
  2. additionthe resulting mass was diluted with water
  3. washThe aqueous layer was washed with DCM (2×50 mL)
  4. extractionIt was extracted with EtOAc (2×100 mL)
  5. washThe EtOAc layer was washed with brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-b511be6e0ad3463f9dcfc286adf7aa2a
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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