Sodium Bicarbonate → 7-(3,4-Dichlorophenyl)-6-(hydroxymethyl)-1,4-oxazepan-6-ol monohydrochloride

Temperature

80 °C

Bismuth(III)trifluoromethanesulfonate (228 mg) was added to a mixed solution of tert-butyl (3RS,4SR)-4-(3,4-dichlorophenyl)-1,5-dioxa-8-azaspiro[2.6]nonane-8-carboxylate (59 mg) in THF/water (v/v=4/1, 5 mL), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 4 mL) of hydrogen chloride in ethyl acetate. The solvent was evaporated under reduced pressure. To a solution of the residue in THF (4 mL) were added triethylamine (0.033 mL) and di-tert-butyl dicarbonate (52 mg), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate, and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, 8 M aqueous sodium hydroxide solution (3 mL) was added, and the mixture was stirred at 90° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate. The solvent was evaporated under reduced pressure to give the title compound (7 mg).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additionTo the residue was added a solution (4 M, 4 mL) of hydrogen chloride in ethyl acetate
6. customThe solvent was evaporated under reduced pressure
7. additionTo a solution of the residue in THF (4 mL) were added triethylamine (0.033 mL) and di-tert-butyl dicarbonate (52 mg)
8. stirringthe mixture was stirred at room temperature for 1 hr
9. additionWater was added to the reaction mixture
10. extractionthe mixture was extracted with ethyl acetate
11. washThe extract was washed with brine
12. dry with materialdried over anhydrous sodium sulfate
13. customThe solvent was evaporated under reduced pressure
14. additionTo the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate
15. stirringthe mixture was stirred at room temperature for 30 min
16. customThe solvent was evaporated under reduced pressure, 8 M aqueous sodium hydroxide solution (3 mL)
17. additionwas added
18. stirringthe mixture was stirred at 90° C. overnight
19. additionWater was added to the reaction mixture
20. extractionthe mixture was extracted with ethyl acetate
21. washThe extract was washed with brine
22. dry with materialdried over anhydrous sodium sulfate
23. customThe solvent was evaporated under reduced pressure
24. additionTo the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate
25. customThe solvent was evaporated under reduced pressure

ORD record

ord-dc72534316254d24a41704d10031df0c

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722662B2