Methyl iodide → HCID 58169916, compound

Participants

Reaction Steps

To a solution of 1-(1,1-dimethylethyl) 2-methyl(2S,5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-1,2-dicarboxylate (Intermediate 43, 1 g, 1.421 mmol) in dry Tetrahydrofuran (THF) (16 ml) at −78° C. LiHMDS 1M in THF (2.132 ml, 2.132 mmol) was added and the reaction mixture was stirred for 10 mins at r.t. iodomethane (0.355 ml, 5.68 mmol) was then added and the reaction mixture was stirred for 30 mins at r.t. The reaction was quenched with brine (1 ml), diluted with water (10 ml) and extracted with ethyl acetate (3×30 ml). Combined organic layers were dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in Dichloromethane (15 ml) and the stirring solution was cooled at 0° C. TFA (5 ml, 64.9 mmol) was added and the reaction mixture was stirred at 0° C. for 1.30 h. The solvent and the excess of TFA were evaporated in vacuo. The residue was dissolved in 20 ml of ethyl acetate and washed with NaHCO3 sat. sol. (5 ml). The organic layer was dried, filtered and evaporated and the residue was purified by flash chromatography on silica gel using a Biotage SNAP 50 g as column and Cyclohexane to Cyclohexane/Ethyl acetate 1:1 as eluent affording the title compounds:

Provenance & Evidence