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

Temperature

-15 °C

(-)-(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.

1. customthe mixture was subjected to 30 minutes of reaction
2. washThe reaction solution was washed with water
3. dry with materialdried over anhydrous magnesium sulfate
4. customThen, the solvent was evaporated under reduced pressure
5. dissolutionThe resulting residue was dissolved in 63 ml of N,N-dimethylformamide
6. addition5.0 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
7. stirringthe mixture was stirred at room temperature for 2 hours
8. additionThen, 2.02 ml of diethylamine was added
9. customthe mixture was subjected to 20 minutes of reaction at room temperature
10. temperaturecooling
11. stirringthe mixture was stirred at room temperature for 1.5 hours
12. extractionthe mixture was extracted with ethyl acetate
13. washThe extract was washed with brine
14. dry with materialdried over anhydrous magnesium sulfate
15. customThe solvent was evaporated under reduced pressure
16. customthe resulting residue was purified by aminopropylated silica gel medium pressure liquid column chromatography (eluent: ethyl acetate)

ORD record

ord-18bd0749565d4bd9b0a097bebb44d597

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06133266