Borane;tetrahydrofuran → (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

Participants

Reaction Steps

(S)-(−)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaboro-borane [(S)-2-methyl-CBS-oxazaborolidine] (1.0 M in tetrahydrofuran, 1.06 mL, 1.06 mmol) was dissolved in anhydrous tetrahydrofuran (53.1 mL, distilled from sodium/benzophenone ketyl). To this solution was simultaneously added a solution of 3-[4-(5H,1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methyl-phenyl]-2-methyl-cyclohex-2-enone of Example 4 (2.18 g, 5.31 mmol) in anhydrous tetrahydrofuran (20 mL) via syringe pump (1.6 mL/min) and borane-tetrahydrofuran complex (1.0 M in tetrahydrofuran, 3.19 mL, 3.19 mmol) at a rate such that enone addition was complete upon addition of approximately ⅔ of the borane-tetrahydrofuran complex. Upon completion of the borane-tetrahydrofuran complex addition, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with 1 N sodium hydroxide, 1 N hydrochloric acid and brine and dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexane followed by reprecipitation from diethyl ether upon addition of petroleum ether, to afford 2.02 g of the title compound as a white solid, [α]589=+34.30 (c=1, chloroform). Analytical HPLC (Chiralpak AD, 4.6×250 mm, 50% ethanol/hexane, 0.5 mL/min.) indicated an enantiomeric excess of 96.4%.

Provenance & Evidence