Methyl iodide → 10-{4-[(3R)-3-Methoxy-2-methylcyclohex-1-en-1-yl]-3-methylbenzoyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Participants

Reaction Steps

(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-((3R)-3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-methanone of Example 41 (0.125 g, 0.303 mmol) was dissolved in anhydrous tetrahydrofuran (3.0 mL) followed by addition of sodium hydride (0.008 g, 0.333 mmol). After hydrogen gas evolution ceased (5 minutes), methyl iodide (0.038 mL, 0.606 mmol) was added and the reaction stirred for 30 minutes. Additional sodium hydride (0.008 g, 0.333 mmol) was added and stirring continued overnight. The reaction was quenched with saturated ammonium chloride (50 mL) and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. Purification of the residue by flash column chromatography, eluting with 30% ethyl acetate in hexane, followed by recrystallization from petroleum ether afforded the title compound (0.120 g) as white crystals, m.p. 127–128° C.; [α]D=+45.65 (c=1.0, chloroform). Single crystal X-ray crystallography established the absolute configuration as the (R)-isomer.

Provenance & Evidence