Hydrochloric Acid → 4-[(2S)-2-methylpiperidin-1-yl]-3-(trifluoromethyl)benzoic acid

HRID 400769Notes

Reaction equation

[CH3:1][C@H: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]>O>[CH3:1][C@H: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

Conditions

Temperature: 100 °C

Procedure

4-[(2S)-2-methylpiperidin-1-yl]-3-(trifluoromethyl)benzonitrile (1.40 g; 5.22 mmol; 1 eq.) was dissolved in MeOH (7 mL) to which was added NaOH (5 N solution in water, 7 mL). The reaction mixture was heated to 100° C. for 7 hours. The reaction mixture was acidified to pH 2 with 5N HCl solution in water. The resulting precipitate was filtered and washed with water to give a light brown solid. It was recrystallized from Et2O/cHex to give a beige solid (851 mg; 57% over 2 steps). 1H NMR (DMSO-d6) δ 13.29 (s, 1H), 8.23-8.12 (m, 2H), 7.68 (d, J=8.4 Hz, 1H), 3.07 (m, 1H), 2.94-2.81 (m, 1H), 2.61-2.45 (m, 2H), 1.75 (m, 1H), 1.67-1.18 (m, 4H), 0.71 (d, J=6.1 Hz, 3H). HPLC (Method A), Rt 4.79 min (Purity: 99.9%). LC/MS (Method B): 286.2 (M+H)−; 288.0 (M+H)+.

Workup

filtrationThe resulting precipitate was filtered
washwashed with water
customto give a light brown solid
customIt was recrystallized from Et2O/cHex
customto give a beige solid (851 mg; 57% over 2 steps)

Sources & evidence

ORD record: ord-6ef96531d4734c8e9ae4116759031d62
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741923B2

Reaction notes

Loading…