Ammonium Chloride → HCID 57941419, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[(4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-3-oxo-2,3,4,5,6,7-hexahydro-4,7-methano-indazol-1-ylmethyl]-benzoic acid methyl ester (Example 104; 189 mg, 0.42 mmol) and pulverized sodium borohydride (102 mg, 2.7 mmol) in tetrahydrofuran (2 mL) was heated at 65° C. for 15 min. Methanol (2 mL) was added dropwise over a period of 2 min and gas evolution was noted. The mixture was heated at 65° C. for 1 h, and then an additional portion of methanol (1 mL) was added. The mixture was heated at 65° C. for 1 h, and then an additional portion of sodium borohydride (ca. 50 mg) was added. The mixture was heated at 65° C. for 1 h, and then an additional portion of sodium borohydride (ca. 50 mg) was added. The mixture was heated at 65° C. for 1 h, and then it was cooled to room temperature. Saturated aqueous ammonium chloride (6 mL) and dichloromethane (30 mL) were added. The mixture was stirred at room temperature for 10 min. 1:1 Water/brine (20 mL) was added and the mixture was extracted with dichloromethane (3×30 mL). The combined organic extracts were dried (magnesium sulfate), filtered, and evaporated. The residue was purified using an ISCO 12 g column, eluting with 75-100% ethyl acetate/hexanes. Fractions containing the product were concentrated, co-evaporated with ether and petroleum ether, and then dried under high vacuum at 50° C. overnight give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(4-hydroxymethyl-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (76 mg, 43%) as a white solid. ES(+)-MS (M+H) 425.

Provenance & Evidence