Tetrahydrofuran → HCID 89994499, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (33, R1=4-Fluorophenyl, R3=Trifluoromethyl) (79 mg, 0.158 mmol) was dissolved in THF (2 mL) and cooled to about 0° C. under nitrogen. The mixture was treated dropwise with DIBAL-H (1M in cyclohexane, 0.90 mL, 0.90 mmol). The reaction was stirred at about 0° C. for about 2 h, then quenched by addition of 6% acetic acid in sat. aq. sodium acetate solution (3 mL). The reaction was concentrated to about 3 mL volume and extracted with DCM (2×20 mL). The organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Intermediate LC/MS, method 3, Rt=3.14 min, MS m/z 537 (M+H)+. The residue was dissolved in EtOH (3 mL) and treated with NaBH4 (18 mg, 0.47 mmol) at rt for about 1 h. The reaction was quenched with aq. NH4Cl solution (2 mL) and stirred about 15 min at rt. The mixture was further diluted with water (2 mL) and extracted with DCM (2×5 mL). The combined DCM layers were washed with water, dried over Na2SO4, filtered and concentrated under reduced pressure to yield (3R,4aR,12bS)-9-(4-fluorophenyl)-12b-(hydroxymethyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol), (37, R1=4-Fluorophenyl, R3=Trifluoromethyl) (85 mg, 100%) as a glass: LC/MS, method 3, Rt=3.02 min, MS m/z 539 (M+H)+. The residue was used in step #2 without further purification.

Provenance & Evidence