Acetic Acid → HCID 15985540, compound

Participants

Reaction Conditions

Reaction Steps

(5R,7S)-4-(cyclohexylamino)-1-(3-fluorophenyl)-8-(3-isopropoxybenzyl)-7-methyl-1,3,8-triazaspiro[4.5]dec-3-en-2-one (11-10, 0.5 g, 0.1 mmoles) was dissolved in THF (2 mL) in an oven-dried flask and the solution was cooled under nitrogen to −78° C. in a dry ice/acetone bath. To the cooled reaction was added a 1 M solution of Lithium bis(trimethylsilyl)amide in THF (0.3 mL, 0.3 mmoles) dropwise, and the solution was warmed to −20° C. for 10 min. The solution was cooled to −50° C. and iodomethane (0.014 g, 0.1 mmole) was added and the reaction stirred for 30 min at −50° C. The reaction was then allowed to warm to rt. A drop of acetic acid was added and the volume was reduced. The residue was partitioned between saturated aqueous sodium bicarbonate (5 mL) and methylene chloride (5 mL). The organic layer was dried over sodium sulfate, filtered and reduced to a residue which was chromatographed on silica gel eluting with a gradient elution of 100% methylene chloride going to 30% methylene chloride/methanol/10% NH4OH solution over 20 min. The desired fractions were combined and the solvents removed to give the product.

Provenance & Evidence