Dimethyl Sulfoxide → HCID 67778374, compound

Temperature

100 °C

A mixture of 2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-(fluoromethyl)ethyl methanesulfonate (97.3 mg), sodium azide (29.7 mg) and dimethyl sulfoxide (2 mL) was stirred at 100° C. for 4 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was mixed with triphenylphosphine (71.8 mg), THF (3 mL) and water (1 mL), and the obtained mixture was stirred at 90° C. for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was mixed with acetic anhydride (1 mL), triethylamine (1 mL) and ethyl acetate (3 mL), and the obtained mixture was stirred at 60° C. overnight. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate). The obtained residue was separated by HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)). A saturated aqueous sodium hydrogen carbonate solution was added to the obtained fraction, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as white crystals (52.3 mg).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe obtained organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customthe solvent was evaporated under reduced pressure
5. additionThe residue was mixed with triphenylphosphine (71.8 mg), THF (3 mL) and water (1 mL)
6. stirringthe obtained mixture was stirred at 90° C. for 2 hr
7. additionWater was added to the reaction mixture
8. extractionthe mixture was extracted with ethyl acetate
9. washThe obtained organic layer was washed with saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customthe solvent was evaporated under reduced pressure
12. additionThe residue was mixed with acetic anhydride (1 mL), triethylamine (1 mL) and ethyl acetate (3 mL)
13. stirringthe obtained mixture was stirred at 60° C. overnight
14. customThe solvent was evaporated under reduced pressure
15. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
16. customThe obtained residue was separated by HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA))
17. additionA saturated aqueous sodium hydrogen carbonate solution was added to the obtained fraction
18. extractionthe mixture was extracted with ethyl acetate
19. washThe obtained organic layer was washed with saturated brine
20. dry with materialdried over anhydrous magnesium sulfate
21. customthe solvent was evaporated under reduced pressure

ORD record

ord-3d99ba6d07e444829f0ecd9a4d8ced67

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729102B2