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

HRID 400735Notes

Reaction equation

HRID 400735 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:15]=[CH:14][C:11]([C:12]#N)=[CH:10][C:9]=1[C:16]([F:19])([F:18])[F:17].[OH-:20].[Na+].Cl.C[OH:24]>>[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:15]=[CH:14][C:11]([C:12]([OH:24])=[O:20])=[CH:10][C:9]=1[C:16]([F:19])([F:18])[F:17]

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
100 °C

Procedure

4-(2-methylpiperidin-1-yl)-3-(trifluoromethyl)benzonitrile obtained in step 1 (28 g; 104.37 mmol) was dissolved in MeOH (280 mL) to which was added sodium hydroxide (336 mL; 5 M) and the reaction mixture was heated at 100° C. for 7 h. After this time, reaction mixture was cooled to 0° C. and acidified to pH ˜2 with HCl (5N). Product precipitated as a white solid that was filtered, washed with water and dried under vacuum to give the title compound as a white powder (27.50 g; 91%). 1H NMR (DMSO-d6) δ 13.30 (bs, 1H), 8.20-8.14 (m, 2H), 7.68 (d, J=8.2 Hz, 1H), 3.08 (m, 1H), 3.10-3.06 (m, 1H), 2.90-2.86 (m, 1H), 2.59-2.54 (m, 1H), 1.77-1.25 (m, 6H), 0.72 (d, J=6.0 Hz, 3H). HPLC (Method B) Rt 5.37 min (Purity: 99.8%). LC/MS (Method B): 288.2 (M+H)+.

Workup

  1. customAfter this time, reaction mixture
  2. temperaturewas cooled to 0° C.
  3. customProduct precipitated as a white solid
  4. filtrationthat was filtered
  5. washwashed with water
  6. customdried under vacuum

Sources & evidence

ORD record
ord-b04e9abea16e4dd19fc3614fd6df0e5f
Source dataset
uspto-grants-2014_06
Patent number
US08741923B2

Reaction notes

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