Hydrochloric Acid → HCID 86732224, compound

(R)-N-((2S,4S)-2-(2,3-difluorophenyl)-1,5,5,5-tetrafluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (2.48 g, 6.34 mmol) was dissolved in dichloromethane (12.0 mL) and MeOH (4.0 mL). To this solution was added hydrogen chloride, 4M in 1,4-dioxane (12.0 mL, 48.0 mmol). After stirred for 10 min, the mixture was concentrated, diluted with dichloromethane and washed with 1N NaOH followed by brine. The organic layer was dried over Na2SO4 and then filtered. The filtrate was concentrated and dried to afford (2S,4S)-4-amino-4-(2,3-difluorophenyl)-1,1,1,5-tetrafluoropentan-2-ol as colorless oil. This crude product was dissolved in THF (60 ml) and then treated with benzoyl isothiocyanate (0.938 mL, 6.97 mmol). After stirred for 1.5 h, triethylamine (1.058 mL, 7.60 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hcl (1.336 g, 6.97 mmol) were added, and the resulted reaction mixture was brought to 70° C. for 2 h. Reaction mixture was partitioned between EtOAc and water. The separated organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and purified by silica gel column (0-20% EtOAc/hexane) to afford N-((4S,6S)-4-(2,3-difluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (2.22 g, 5.33 mmol, 84% yield) as white solid. MS m/z=417.1 [M+H]+. Calculated for C19H14F6N2O2: 416.3

1. concentrationthe mixture was concentrated
2. additiondiluted with dichloromethane
3. washwashed with 1N NaOH
4. dry with materialThe organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated
7. customdried

ORD record

ord-f1603099ea1c45079f45e0261ba2b8e3

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2