Water → (-)-(2R)-2-[(2S)-2-[[2-(2,2-dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)-2-hydroxyethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide

Participants

Reaction Conditions

Reaction Steps

(-)-(1R)-1-(2,2-Dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)2-[((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)amino]-ethanol (5.15 g) and 11.3 ml of N,N-diisopropylethylamine were added to 125 ml of methylene chloride, a solution of 5.51 ml of trifluoroacetic anhydride in 16 ml of methylene chloride was added to the resulting suspension with stirring at -15° C., and the mixture was subjected to 30 minutes of reaction. The reaction solution was washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated under reduced pressure. The resulting residue was dissolved in 63 ml of N,N-dimethylformamide, 5.0 g of molecular sieves 4A powder, 3.24 g of 2-bromo-N,N-dimethyl-acetamide and 19.0 g of cesium carbonate were added to the solution, and the mixture was stirred at room temperature for 2 hours. Then, 2.02 ml of diethylamine was added and the mixture was subjected to 20 minutes of reaction at room temperature. After adding 90 ml of water and 180 ml of methanol to the reaction solution under ice-cooling, the mixture was stirred at room temperature for 1.5 hours. Then, brine was added and the mixture was extracted with ethyl acetate. The extract was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by aminopropylated silica gel medium pressure liquid column chromatography (eluent: ethyl acetate) to give 3.22 g of (-)-(2R)-2-[(2S)-2-[[2-(2,2-dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)-2-hydroxyethyl]amino]-1,2,3,4-tetrahydronaphthalen-7-yloxy]-N,N-dimethylacetamide in an oily form.

Provenance & Evidence