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)-(−)-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 (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-(2-methyl-3-oxo-cyclohex-1-en-1-yl)-3-methyl-phenyl]-methanone of Example 4 (2.18 g, 5.31 mmol) in anhydrous tetrahydrofuran (20 mL) via syringe pump (1.6 mL/min.) and borane-tetrahydrofuran (1.0 M in tetrahydrofuran, 3.19 mL, 3.19 mmol) at a rate such that enone addition was complete upon addition of approximately 2/3 of borane-tetrahydrofuran. Upon completion of borane-tetrahydrofuran addition, the reaction mixture was diluted with water (250 mL) and extracted with ethyl acetate. The combined extracts were washed with 1 N sodium hydroxide, 1N hydrochloric acid, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (silica, 50% ethyl acetate in hexane) to afford the title compound (2.02 g) as a white solid. Analytical HPLC (Chiralpak AD, 4.6×250 mm, 50% ethanol in hexane, 0.5 mL/min.) indicated an enantiomeric excess of 96.4%.

Provenance & Evidence