Acetic Anhydride → HCID 59556390, compound

To an ice cooled solution of 365 mg 2,2-Difluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-but-3-en-1-ol in 10 ml pyridine were added 5 ml acetic acid anhydride. The ice bath was removed and the reaction mixture stirred at room temperature for one hour. The ice was added and the reaction mixture diluted by addition of 100 ml dichloromethane. The organic layer was separated and washed with 50 ml water, 1 M HCl, saturated NaHCO3 solution and brine. Then the organic layer was dried over MgSO4 and the solvent removed in vacuo. The resulting residue was dissolved in 30 ml diethyl ether (flask 1). 246 mg palladium, (II) acetate were added and the mixture cooled in an ice bath. In a second flask 4.0 g N-methyl-N-nitroso-p-toluenesulfonamide were suspended in 30 ml ethanol. An argon current was bubbled permanently through flask 2 and afterwards through flask 1. 2N NaOH was added dropwise to flask 2 until dissolution of N-methyl-N-nitroso-p-toluenesulfonamide, then the argon current was stopped. The reaction mixture (flask 1) was stirred at 0° C. for an additional hour. Then 10 ml acetic acid were added and the reaction mixture diluted by addition of 80 ml ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The solvent was removed in vacuo. The resulting residue was dissolved in 20 ml methanol, 1 ml sodium methylate solution (30%) were added and the reaction mixture was stirred at room temperature for one hour. The reaction mixture was then neutralized by addition of acetic acid, the solvent was removed in vacuo and the residue purified by reversed phase HPLC to obtain 120 mg 2-Cyclopropyl-2,2-difluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol as lyophilisate.

1. customThe ice bath was removed
2. additionThe ice was added
3. additionthe reaction mixture diluted by addition of 100 ml dichloromethane
4. customThe organic layer was separated
5. washwashed with 50 ml water, 1 M HCl, saturated NaHCO3 solution and brine
6. dry with materialThen the organic layer was dried over MgSO4
7. customthe solvent removed in vacuo
8. dissolutionThe resulting residue was dissolved in 30 ml diethyl ether (flask 1)
9. addition246 mg palladium, (II) acetate were added
10. temperaturethe mixture cooled in an ice bath
11. customIn a second flask 4.0 g N-methyl-N-nitroso-p-toluenesulfonamide were suspended in 30 ml ethanol
12. customAn argon current was bubbled permanently through flask 2
13. addition2N NaOH was added dropwise to flask 2
14. dissolutionuntil dissolution of N-methyl-N-nitroso-p-toluenesulfonamide
15. stirringThe reaction mixture (flask 1) was stirred at 0° C. for an additional hour
16. additionThen 10 ml acetic acid were added
17. additionthe reaction mixture diluted by addition of 80 ml ethyl acetate
18. washThe organic layer was washed with brine
19. dry with materialdried over MgSO4
20. customThe solvent was removed in vacuo
21. dissolutionThe resulting residue was dissolved in 20 ml methanol
22. addition1 ml sodium methylate solution (30%) were added
23. stirringthe reaction mixture was stirred at room temperature for one hour
24. additionThe reaction mixture was then neutralized by addition of acetic acid
25. customthe solvent was removed in vacuo
26. customthe residue purified by reversed phase HPLC

ORD record

ord-59a2ed4b103949edbf9493929a0e50ef

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834030B2