Tetrahydrofuran → tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate

To a solution of tert-butyl [(2S)-2-{[4-bromo-2-(hydroxymethyl)thiophen-3-yl]oxy}propyl]carbamate (1.83 g), methanesulfonyl chloride (0.58 ml,) and THF (50 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (1.65 ml,), and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution (30 mL) of the residue in DMF was added sodium hydride (60% in oil, 0.4 g) at room temperature, and the mixture was stirred for 30 min. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 5→20% ethyl acetate/hexane) to give the title compound (1.17 g, 67%) as a colorless oil.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with water and saturated brine
3. dry with materialdried over magnesium sulfate
4. customthe solvent was evaporated under reduced pressure
5. additionTo a solution (30 mL) of the residue in DMF was added sodium hydride (60% in oil, 0.4 g) at room temperature
6. stirringthe mixture was stirred for 30 min
7. additionTo the reaction mixture was added saturated aqueous ammonium chloride solution
8. extractionthe mixture was extracted with ethyl acetate
9. washThe extract was washed with water and saturated brine
10. dry with materialdried over magnesium sulfate
11. customthe solvent was evaporated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (solvent gradient; 5→20% ethyl acetate/hexane)

ORD record

ord-9a9192d4a6834a2ab630d26b5c40180a

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916549B2