Diisopropylethylamine → (3R,5R)-1-(((S)-7-(trifluoromethyl)chroman-4-yl)carbamoyl)-5-(4-(4-chlorobenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)pyrrolidin-3-yl acetate

Participants

Reaction Steps

To a stirring solution of triphosgene (23 mg, 0.078 mmol) in dichloromethane (0.5 ml) was slowly added dropwise via syringe a premixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (45 mg, 0.21 mmol) and N,N-diisopropylethylamine (0.073 ml, 0.42 mmol) dissolved in dichloromethane (0.8 ml). The reaction mixture was stirred at room temperature for 15 minutes. The isocyanate thereby generated was then treated dropwise with a solution of (3R,5R)-5-(4-(4-chlorobenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)pyrrolidin-3-yl acetate hydrochloride from Step E (70 mg, 0.21 mmol) and N,N-diisopropylethylamine (0.073 ml, 0.42 mmol) dissolved in dichloromethane (0.8 ml). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated to dryness, diluted with EtOAc, washed with 10% aqueous KHSO4, 5% aqueous NaHCO3, and brine, dried (Na2SO4), filtered and concentrated to yield an oil (120 mg, 100%) which was used without further purification in the next reaction.

Provenance & Evidence