Dimethyl Sulfoxide → HCID 86727212, compound

Temperature

-30 °C

To a solution of DMSO (0.193 g, 2.46 mmol) in anhydrous DCM (10 mL) at −78° C. under N2 was added oxalyl chloride (0.268 g, 2.11 mmol) slowly, and the mixture was stirred at −30° C. for 45 min. The mixture was then cooled at −78° C., and a solution of ((3aR,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-2-(dimethylamino)-3a,4,5,6,7,7a-hexahydrobenzo[d]thiazol-6-yl)methanol (14) (0.330 g, 0.704 mmol) in anhydrous DCM (5 mL) was added slowly. After stirring at −30° C. for 2 h the reaction mixture was cooled back at −78° C., and triethylamine (0.50 g, 5.0 mmol) was added. The mixture was stirred at −30° C. for another 30 min, and then quenched with water (30 mL). The organic layer was collected, and the aqueous was extracted with DCM (3×20 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure to give a sticky pale yellow foam. Under N2 the pale yellow foam was dissolved in anhydrous THF (15 mL), and MeMgBr (1.4 M in THF/toluene, 1.5 mL, 2.1 mmol) was added. After addition the mixture was stirred at room temperature for 1.5 h. The reaction was quenched with saturated aqueous NaHCO3 (20 mL), and then extracted with DCM (3×15 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash column chromatography (EtOAc), affording mixed 15a & 15b as a sticky pale yellow foam (0.23 g, 74%) with a ratio of 15a:15b=1:3 based on 1H NMR.

1. temperatureThe mixture was then cooled at −78° C.
2. stirringAfter stirring at −30° C. for 2 h the reaction mixture
3. temperaturewas cooled back at −78° C.
4. stirringThe mixture was stirred at −30° C. for another 30 min
5. customquenched with water (30 mL)
6. customThe organic layer was collected
7. extractionthe aqueous was extracted with DCM (3×20 mL)
8. extractionThe combined extract
9. dry with materialwas dried over anhydrous Na2SO4
10. filtrationAfter filtration the solvent
11. customwas evaporated under reduced pressure
12. customto give a sticky pale yellow foam
13. additionAfter addition the mixture
14. stirringwas stirred at room temperature for 1.5 h
15. customThe reaction was quenched with saturated aqueous NaHCO3 (20 mL)
16. extractionextracted with DCM (3×15 mL)
17. extractionThe combined extract
18. dry with materialwas dried over anhydrous Na2SO4
19. filtrationAfter filtration the solvent
20. customwas evaporated under reduced pressure
21. customthe residue was purified on silica gel by flash column chromatography (EtOAc)
22. customaffording

ORD record

ord-949811808e9d43e4b5df4b27d20ae061

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126957B2