Diisopropylethylamine → (R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one

Participants

Reaction Steps

To a solution of (R)-2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino) propylthio)acetic acid (3.3 g, 6.99 mmol, Eq: 1.00) and N,N-diisopropylethylamine (2.71 g, 3.66 ml, 21.0 mmol, Eq: 3.0) in ethyl acetate (194 ml) was added at 23° C. 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate) (6.67 g, 6.23 ml, 10.5 mmol, Eq: 1.5) and the colourless reaction solution was stirred at 23° C. for 2 hours. The reaction mixture was washed with sat NaHCO3-sol., water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give the nearly pure (R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one (2.95 g, 6.49 mmol, 92.9% yield) as a colourless oil, which crystallized in the fridge and was used without further purification. MS (ISP): m/z=454.0 [M+H]+ and 456.1 [M+2+H]+.

Provenance & Evidence