Water → HCID 18472606, compound

A solution of methyl 7-bromo-5-oxo-2,3,4,5-tetrahydro-1-benzothiepine-4-carboxylate (24.94 g) in THF (200 ml) was cooled to −20° C., and to the mixture was added dropwise a solution of sodium boro hydride (2.99 g) in methanol (30 ml). While the temperature of the mixture was kept at −15 to 20° C., the mixture was stirred for 1 hour. To the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue (24.38 g) was dissolved in THF (200 ml). To the mixture was added triethylamine (26 ml) and then to the mixture was added dropwise at 0° C. methanesulfonyl chloride (9.2 ml). The mixture was stirred at 0° C. for 30 minutes and then at room temperature for 15 hours. To the mixture was added dropwise 1,8-diaza-bicyclo[5,4,0]-7-undecene (17.9 g), and the mixture was stirred for 3 hours. To the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated, and the residue was purified with column chromatography (ethyl acetate/hexane=1:10). Under reduced pressure, the mixture was concentrated, and the resulting crystals were recrystallized from ethyl acetate/hexane to give pale yellow crystals of methyl 7-bromo-2,3-dihydro-1-benzothiepine-4-carboxylate (11.00 g).

1. customwas kept at −15 to 20° C.
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried with magnesium sulfate
5. customUnder reduced pressure, the solvent was evaporated
6. dissolutionthe residue (24.38 g) was dissolved in THF (200 ml)
7. additionTo the mixture was added triethylamine (26 ml)
8. additionto the mixture was added dropwise at 0° C. methanesulfonyl chloride (9.2 ml)
9. stirringThe mixture was stirred at 0° C. for 30 minutes
10. waitat room temperature for 15 hours
11. additionTo the mixture was added dropwise 1,8-diaza-bicyclo[5,4,0]-7-undecene (17.9 g)
12. stirringthe mixture was stirred for 3 hours
13. additionTo the mixture was added water
14. extractionthe mixture was extracted with ethyl acetate
15. washThe organic layer was washed with water and saturated brine
16. dry with materialdried with magnesium sulfate
17. concentrationUnder reduced pressure, the mixture was concentrated
18. customthe residue was purified with column chromatography (ethyl acetate/hexane=1:10)
19. concentrationUnder reduced pressure, the mixture was concentrated
20. customthe resulting crystals were recrystallized from ethyl acetate/hexane

ORD record

ord-cf4a27bc995d45b794010e4812c411d8

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06172061B2