Dimethyl Sulfoxide → HCID 15399109, compound

Temperature

-78 °C

Oxalyl chloride (0.34 mL, 3.9 mmol) was added to a solution of dimethyl sulfoxide (0.41 mL, 5.8 mmol) in methylene chloride (10 mL) at −78° C. After 20 min. at −78° C., 3-(benzyloxycarbonyl-amino)-N-[1-(2-fluoro-pyridin4-yl)-2-hydroxy-2-(3-trifluoromethyl-phenyl)ethyl]-N-methyl-propionamide (1.0 g, 1.9 mmol) in methylene chloride (10 mL) was added and the reaction solution was stirred at −78° C. for 2 hrs. Triethylamine (1.3 mL, 9.6 mmol) was added and the cooling bath was removed. The solution was diluted with ethyl acetate (150 mL), washed with aqueous ammonium chloride (75 mL) and brine (75 mL), dried (sodium sulfate), and concentrated. Some non-polar impurities were removed by passing the residue through silica gel, eluting with 50% ethyl acetate in hexane. The ketone was then transferred to a flask containing anhydrous ammonium trifluoroacetate (4 g) using a minimum amount of ether-methylene chloride. The mixture was placed under vacuum to remove the solvent, and then placed in a preheated oil bath (150° C.). Once all solid had melted and efficient stirring was achieved (approx. 10 min.) the formation of the imidazole was found to be complete. The heating bath was removed and the solids were partitioned between ethyl acetate and water (150/50 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated. The product was purified by filtration through silica gel (imidazole is the least polar component) using ethyl acetate to yield 735 mg of a foam.

1. customthe cooling bath was removed
2. additionThe solution was diluted with ethyl acetate (150 mL)
3. washwashed with aqueous ammonium chloride (75 mL) and brine (75 mL)
4. dry with materialdried (sodium sulfate)
5. concentrationconcentrated
6. customSome non-polar impurities were removed
7. washeluting with 50% ethyl acetate in hexane
8. customThe ketone was then transferred to a flask
9. additioncontaining anhydrous ammonium trifluoroacetate (4 g)
10. customto remove the solvent
11. customplaced in a preheated oil bath
12. custom(150° C.)
13. stirringefficient stirring
14. custom(approx. 10 min.)
15. customThe heating bath was removed
16. customthe solids were partitioned between ethyl acetate and water (150/50 mL)
17. dry with materialThe organic layer was dried (sodium sulfate)
18. filtrationfiltered
19. concentrationconcentrated
20. filtrationThe product was purified by filtration through silica gel (imidazole

ORD record

ord-032810264ff94ae985d43c6956ec099d

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06291457B1