反应详情

A mixture of trans-(1,1-diethyl-7-hydroxy-3-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-carbamic acid tert-butyl ester (195.0 g, 0.558 mol), triethylamine (160 mL, 1.1 mol) and ethyl acetate (2000 mL) was stirred at room temperature for 15 min and cooled to 0° C. followed by slow addition of trifluoro-methanesulfonyl chloride (150 g, 0.89 mol) keeping the internal temperature below 4° C. The resulting slurry was stirred at 0° C. for 1 h. Additional triethylamine (16 mL) followed by additional trifluoromethanesulfonyl chloride (15.0 g) was added slowly maintaining a temperature below 5° C. The reaction mixture was stirred at room temperature for an additional hour. Diluted brine (1.0 L) was added and the reaction mixture was stirred for 10 min at room temperature. The layers were separated; the organic layer was washed with diluted NaHCO3 (1.0 L) and then concentrated to −350 mL by rotary evaporation at 28° C. and stirred at room temperature for 30 min. Heptane (700 mL) was added and the resulting slurry was stirred at room temperature for 30 min, cooled to 4° C. and stirred for 1 h. The solids were filtered, washed with heptane, and then dried under vacuum to yield the title compound (193.0 g, >97% purity). The filtrate was concentrated, slurried in an isopropyl acetate and heptane mixture (1:3, 60 mL) over 30 min, filtered and dried to yield additional product (45.0 g, >97% purity).

1. temperaturecooled to 0° C.
2. customthe internal temperature below 4° C
3. stirringThe resulting slurry was stirred at 0° C. for 1 h
4. additionwas added slowly
5. temperaturemaintaining a temperature below 5° C
6. stirringThe reaction mixture was stirred at room temperature for an additional hour
7. stirringthe reaction mixture was stirred for 10 min at room temperature
8. customThe layers were separated
9. washthe organic layer was washed with diluted NaHCO3 (1.0 L)
10. concentrationconcentrated to −350 mL by rotary evaporation at 28° C.
11. stirringstirred at room temperature for 30 min
12. additionHeptane (700 mL) was added
13. stirringthe resulting slurry was stirred at room temperature for 30 min
14. temperaturecooled to 4° C.
15. stirringstirred for 1 h
16. filtrationThe solids were filtered
17. washwashed with heptane
18. customdried under vacuum