Hydrochloric Acid → (S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid

Participants

Reaction Conditions

Reaction Steps

The potassium hydroxide (86 mg, 1.54 mmol) was added to a station (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (102 mg, 0.154 mmol) in ethanol (3 mL) and stirred for 12 h at 90° C. The reaction mixture was neutralized with 1N HCl solution, extracted with EtOAc, and the organic layer was washed with brine, and dried (MgSO4). The crude material was purified by prep HPLC to give (S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid 24.3 mg (25%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.24-7.22 (m, 2H), 7.18-7.12 (m, 4H), 7.10 (t, J=7.7 Hz, 2H), 6.99-6.92 (m, 3H), 5.77 (s, 1H), 4.21 (t, J=6.6 Hz, 2H), 3.47-3.37 (m, 4H), 3.06 (t, J=6.2 Hz, 2H), 2.46-2.44 (m, 2H), 2.42 (s, 3H), 2.01 (s, 3H), 1.66 (t, J=10.6 Hz, 1H), 1.44-1.41 (m, 1H), 1.34-1.22 (m, 3H), 1.09 (m, 9H). UPLC (M+H)=625.4.

Provenance & Evidence