Dimethyl Sulfoxide → Ammonium Hydroxide

Participants

Reaction Steps

To a stirred solution of oxalyl chloride (68 mg) in dry dichloromethane (4 mL) at -60° C., under argon, was added dry dimethyl sulfoxide (0.107 mL) dropwise. The resulting mixture was stirred for 5 min, then added to a solution of (±)-cis-1,3-dihydro-1-(1-{4-[(5-pyrimidinyl)hydroxymethyl]cyclohex-1-yl}piperidin-4-yl)-2H -benzimidazol-2-one (112 mg) in dichloromethane (5 mL) at -60° C. The reaction mixture was stirred for 20 min at -60° C., then triethylamine (0.54 mL) was added and the solution was allowed to warm to room temperature. Water was added and the mixture stirred for a further 10 min, after which saturated sodium carbonate was added and the mixture was extracted with dichloromethane (3×20 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo. Purification by preparative TLC on silica eluting with chloroform; 7% methanol; 1% NH4OH, followed by a second purification eluting with dichloromethane; 10% methanol; 1% NH4OH yielded trans-1,3-dihydro-1-{1-[4-(5-pyrimidinylcarbonyl)cyclohex-1-yl]piperidin-4-yl}-2H-benzimidazol-2-one: 1H NMR (400 MHz, CDCl3 ; CD3 OD) 9.34 (s, 1H), 9.30 (s, 2H), 7.43 (m, 1H), 7.11-7.04 (m, 3H), 4.40 (tt, 1H), 3.36 (m, 1H), 3.28 (d, 2H), 2.73-2.57 (m, 5H), 2.24-2.10 (m, 4H), 1.90 (m, 2H), 1.633 (m, 4H). m/z (FAB): 406 (MH+). The hydrochloride salt was precipitated from ethanol/chloroform: analysis calculated for C23H27N5O2.2 HCl.0.75 H2O.0.35 C2 H5OH C: 56.03, H: 6.47, N: 13.78; found C: 56.03, H: 6.14, N: 13.76.

Provenance & Evidence