Hydrochloric Acid → 4-(2-Methylpiperidin-1-YL)-3-(trifluoromethyl)benzoic acid

HRID 1630977Notes

Reaction equation

HRID 1630977 reaction equation
[OH-:1].[Na+].[CH3:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:17]=[CH:16][C:13]([C:14]#N)=[CH:12][C:11]=1[C:18]([F:21])([F:20])[F:19].Cl.C[OH:24]>>[CH3:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:17]=[CH:16][C:13]([C:14]([OH:24])=[O:1])=[CH:12][C:11]=1[C:18]([F:21])([F:20])[F:19]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 585541304-(2-Methylpiperidin-1-YL)-3-(trifluoromethyl)benzonitrile

Product 1

HCID 594956554-(2-Methylpiperidin-1-YL)-3-(trifluoromethyl)benzoic acidYield 91%

Conditions

Temperature
0 °C

Procedure

A 5N aqueous solution of sodium hydroxide (336 mL, 1.68 mol) was added into a solution of 4-(2-methylpiperidin-1-yl)-3-(trifluoromethyl)benzonitrile (28.0 g, 104.4 mmol) in MeOH (280 mL) and the resulting mixture was heated at reflux for 7 hours. The reaction mixture was cooled to 0° C. and acidified to pH 2 with a 5N aqueous solution of HCl. The precipitate was filtered, washed with water and dried under vacuum to give the title compound as a white powder (27.5 g, 91%). HPLC (Method A), Rt 5.4 min (purity: 99.8%). UPLC/MS, M+(ESI): 288.2, M−(ESI): 286.2. 1H NMR (DMSO-d6, 300 MHz) δ 13.30 (bs, 1H), 8.17 (m, 2H), 7.68 (d, J=8.2 Hz, 1H), 3.08 (m, 1H), 3.08 (m, 1H), 2.88 (m, 1H), 2.57 (m, 1H), 1.77-1.25 (m, 6H), 0.72 (d, J=6.0 Hz, 3H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 7 hours
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. customdried under vacuum

Sources & evidence

ORD record
ord-65389ab86aef42d4a9f94f8c96641786
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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