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

HRID 2410479Notes

Reaction equation

HRID 2410479 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 (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 hours. Solvents were removed under vacuum and the resulting mass was diluted with water. The aqueous layer was washed with DCM (2×50 mL), and then acidified with a concentrated aqueous solution of 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), 8.17 (m, 2H), 7.69 (d, 1H), 3.08 (m, 1H), 2.88 (m, 1H), 2.50 (m, 1H), 1.90 (m, 2H), 1.75 (m, 2H), 1.45 (m, 1H), 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-fdbc3fadb094466489bb6d2e9152f11f
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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