Carbonocyanidic acid, methyl ester → (4-(1-(cyclopropylmethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)-1-tritylpiperidin-4-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(cyclopropylmethyl)-2-neopentyl-5-(1-tritylpiperidin-4-ylsulfonyl)-1H-benzo[d]imidazole (STEP E, 2.05 g, 3.24 mmol) in tetrahydrofuran (60 mL) at −60° C. was added lithium diisopropylamide (1.8 mol/L heptane/tetrahydrofuran/ethylbenzene solution, 2.34 mL, 4.22 mmol). After the mixture was warmed up to −40° C. over a period of 20 min and then stirred for 40 min at the same temperature, methyl cyanoformate (828 mg, 9.73 mmol) in tetrahydrofuran (3 mL) was added to the mixture. The mixture was stirred at 0° C. for 1.5 h. The reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate, gradient) to give 4:1 mixture of the title compound and the starting material (2.15 g).

Provenance & Evidence