tert-Butyl acrylate → 3-{4-[4-(4-Cyclohexyl-3-methyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 4-[4-(4-cyclohexyl-3-methyl-phenoxymethyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester (127 mg, 0.27 mmol) in DCM/TFA (1:2 v/v, 3 mL) is stirred for 40 minutes. After concentration, the residue obtained is dissolved in methanol (2 mL). DIEA (130 μL, 1.36 mmol, 5 eq.) and t-butyl acrylate (80 μL, 0.54 mmol, 2 eq.) are added to this solution. The reaction mixture is heated at 90° C. for 30 minutes using microwave irradiation. After concentration, the residue is purified by silica gel chromatography (40% EtOAc in hexanes) to give 3-{4-[4-(4-cyclohexyl-3-methyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid tert-butyl ester. This material is dissolved in DCM/TFA (1:1 v/v, 3 mL), and the solution is stirred at room temperature for 40 minutes. After concentration, the crude product is purified by preparative RP LC-MS to give 3-{4-[4-(4-cyclohexyl-3-methyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid: 1H NMR (CD3OD, 400 MHz) δ 7.41 (d, 2H, J=8 Hz), 7.28 (d, 2H, J=8 Hz), 7.08 (m, 1H), 6.75-6.73 (2H), 5.01 (s, 2H), 3.69 (d, 2H, J=10 Hz), 3.46 (t, 2H, J=7 Hz), 3.18 (m, 2H), 2.95 m, 1H), 2.86 (t, 2H, J=7 Hz), 2.65 (m, 1H), 2.27 (s, 3H), 2.18 (m, 2H), 2.04-1.70 (7H), 1.46-1.30 (5H); MS (ES+): (436.3, M+1)+.

Provenance & Evidence