Tetrahydro-4H-pyran-4-one → 6-chloro-5-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

6-Chloro-5-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D9) (˜0.2 mmol, 60 mg), Ti(iPrO)4 (2 eq., 0.400 mmol, 0.130 ml), tetrahydro-4H-pyran-4-one (2 eq., 0.400 mmol, 40 ul) were stirred together at room temperature for one hour; dry MeOH (2 ml) followed by NaBH3CN (2 eq., ˜30 mgs) were added and the mixture was stirred under argon at room temperature for 3 hours. The crude mixture was subsequently quenched with water (5 ml) and it was firstly purified by SCX followed by chromatography (methanol-NH3-dichloromethane) to yield 6-chloro-5-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 10 mg, 14%, M++H=350, which was converted into the hydrochloride salt using 1M HCl in diethyl ether.