Hydrochloric Acid → HCID 86732238, compound

(R)-N-((2S,4S)-2-(2,3-difluorophenyl)-5,5,5-trifluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (7.18 g, 19.23 mmol) was dissolved in DCM (50 mL) and MeOH (25 mL) to form a clear solution. To this solution was added hydrogen chloride, 4M in 1,4-dioxane (48.1 ml, 192 mmol) via syringe. After stirred for 40 min, the mixture was concentrated, basified with 1N NaOH and diluted with DCM (400 ml) and water (50 ml). The separated organic layer was washed with brine (2×), dried over Na2SO4 and then filtered. The filtrate was concentrated and dried in vacuum to afford (2S,4S)-4-amino-4-(2,3-difluorophenyl)-1,1,1-trifluoropentan-2-ol as white solid with MS+=270 (M+1). This crude product was dissolved in THF (100 ml) and then treated with benzoyl isothiocyanate (2.85 ml, 21.15 mmol). After stirred for 40 min, triethylamine (3.21 ml, 23.08 mmol) and N1-((ethylimino)methylene)-N3,N-3-dimethylpropane-1,3-diamine hydrochloride (4.05 g, 21.15 mmol) were added. The resulted suspension was brought up to 70° C. for 40 min. Then the 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-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (7.0 g, 17.57 mmol, 91% yield) as white solid. MS m/z=399.0 [M+H]+. Calculated for C19H15F5N2O2: 398.3

1. concentrationthe mixture was concentrated
2. additiondiluted with DCM (400 ml) and water (50 ml)
3. washThe separated organic layer was washed with brine (2×)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated
7. customdried in vacuum

ORD record

ord-7407630e7a7747baa9a2322e654275a7

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2