2-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide → HCID 69933055, compound

Temperature

-78 °C

2-{3-(3-Bromophenyl)-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-1-yl}-1-(tert-butyldimethylsilyloxy)ethane (4.2 g, 7.8 mmol) was dissolved in 40 mL of hexane (dried over Na2SO4) and 15 mL THF (freshly distilled from CaH2). The solution was sparged with argon and cooled to −78° C. To the stirred solution was added nBuLi (6.21 mL of a 2.5 M solution in hexanes, 15.5 mmol) and the mixture was stirred for 15 min. LCMS showed incomplete reaction, so more nBuLi (1.0 mL, 2.5 mmol) was added and the mixture was stirred for 10 min. 2-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1.4 g, 7.8 mmol) was dissolved in 10 mL of THF (freshly distilled from CaH2) and cooled to −78° C. The cold solution of sulfinamide was added via cannula into the cold solution of anion. The resulting mixture was stirred for 10 min, then quenched by addition of 20% aqueous NH4Cl solution. The mixture was warmed to ambient temperature and extracted with EtOAc. The EtOAc layer was washed with water and brine, then dried over MgSO4, and the solvents were removed under reduced pressure. The residue was chromatographed on a 120 g silica gel column using 0-100% EtOAc:hexanes over 36 min at 85 mL/min. The product-containing fractions were combined and the solvents were removed under reduced pressure to give N-{3-[3-(1-ethenyl-5-(4-trifluoromethylphenoxy)-1H-pyrazol-3-yl)phenyl]oxetan-3-yl}tert-butylsulfinamide as an oil. Calcd (M+1)+: 506.6. Found: 506.3

1. distillation15 mL THF (freshly distilled from CaH2)
2. customThe solution was sparged with argon
3. additionTo the stirred solution was added nBuLi (6.21 mL of a 2.5 M solution in hexanes, 15.5 mmol) and the mixture
4. customreaction
5. stirringthe mixture was stirred for 10 min
6. distillationfreshly distilled from CaH2) and
7. temperaturecooled to −78° C
8. additionThe cold solution of sulfinamide was added via cannula into the cold solution of anion
9. stirringThe resulting mixture was stirred for 10 min
10. customquenched by addition of 20% aqueous NH4Cl solution
11. temperatureThe mixture was warmed to ambient temperature
12. extractionextracted with EtOAc
13. washThe EtOAc layer was washed with water and brine
14. dry with materialdried over MgSO4
15. customthe solvents were removed under reduced pressure
16. customThe residue was chromatographed on a 120 g silica gel column
17. waithexanes over 36 min at 85 mL/min
18. customthe solvents were removed under reduced pressure

ORD record

ord-fb8e188b19284a1f85219d15f54b7e8b

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871796B2