Ethyl Acetate → 2-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanol

Participants

Reaction Conditions

Reaction Steps

To the solution of 2,2,2-trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide (40 mg, 0.108 mmol) in ethanol (2 mL) was added 1 M NaOH (1 mL, 1.000 mmol). The reaction was heated to 80° C. for 1 hr. Then 10 ml of ethyl acetate was added. Layers were separated, organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The oil was purified on preparative HPLC (5 to 70% AcCN: H2O gradient with 0.1% formic acid modifier). The fractions were collected. The combined fractions were neutralized with aq. NH4OH, concentrated and extracted with ethyl acetate. Organic layer was washed with brine, dried over MgSO4 and evaporated. 2-(4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanol (10 mg, 0.035 mmol, 32.1% yield) was isolated as colorless oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.19-7.28 (m, 2H), 7.10-7.16 (m, 1H), 7.03-7.09 (m, 2H), 3.70 (t, J=6.32 Hz, 2H), 2.95-3.08 (m, 2H), 2.61 (d, J=6.82 Hz, 2H), 2.54 (t, J=6.19 Hz, 2H), 2.25-2.37 (m, 1H), 2.02-2.16 (m, 2H), 1.92 (ddd, J=3.28, 5.87, 9.28 Hz, 1H), 1.69-1.85 (m, 2H), 1.49-1.64 (m, J=3.54, 7.48, 7.48, 14.84 Hz, 1H), 1.20-1.36 (m, 2H), 1.08 (dt, J=4.77, 9.41 Hz, 1H), 1.01 (dt, J=5.59, 7.26 Hz, 1H); LC-MS Rt=0.48 min; MS (ESI): 275.2 [M+H]+.

Provenance & Evidence