Toluene → propan-2-yl 4-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-1-yl]-1-piperidyl]-4-methyl-piperidine-1-carboxylate

Participants

Reaction Steps

A solution of (3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (HCl salt, 99 mg, 0.25 mmol) and diisopropylethylamine (129.3 mg, 1.0 mmol) in dry dichloromethane (5 mL) at 0° C. was added with a solution of 1.0 N isopropyl chloroformate in toluene (0.3 mL, 0.3 mmol) dropwise and stirred at room temperature for 3 h. Saturated NaHCO3 (5 mL) was added followed by dichloromethane (20 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×10 mL). The combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified with preparative LC/MS (high pH) to give the title compound (49 mg, 48%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.95 (s, 3H), 1.21 (d, J=6.25 Hz, 6H), 1.31-1.49 (m, 6H), 1.52-1.64 (m, 1H), 1.65-1.88 (m, 7H), 1.95 (d, J=7.42 Hz, 1H), 2.10-2.20 (m, 2H), 2.26 (d, J=7.81 Hz, 1H), 2.89-3.15 (m, 4H), 3.31-3.44 (m, 2H), 3.42-3.51 (m, 2H), 3.53-3.64 (m, 1H), 4.78-4.90 (m, 1H). MS (M+1): 407.2.

Provenance & Evidence