Lithiumtriethylborohydride → N-[(4aR,6S,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Lithium triethylborohydride (1.13 mL, 1.13 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C27) (60 mg, 0.11 mmol) in tetrahydrofuran (4 mL). The reaction mixture was allowed to stir at room temperature for 16 hours and then partitioned between ethyl acetate (25 mL) and a saturated aqueous solution of sodium bicarbonate (50 mL). The layers were separated and the aqueous layer was extracted further with ethyl acetate (3×25 mL). The combined organics were then washed sequentially with water (100 mL) and with brine (100 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield a white solid. The organic crude was re-dissolved in dichloromethane (20 mL) and the resulting solution was washed with 1 N sodium hydroxide (3×25 mL), water (100 mL), and brine (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the product as an orange solid (60 mg), which was taken directly to the following step. LCMS m/z 514 [M+H+].

1. custompartitioned between ethyl acetate (25 mL)
2. customThe layers were separated
3. extractionthe aqueous layer was extracted further with ethyl acetate (3×25 mL)
4. washThe combined organics were then washed sequentially with water (100 mL) and with brine (100 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customto yield a white solid
9. washthe resulting solution was washed with 1 N sodium hydroxide (3×25 mL), water (100 mL), and brine (100 mL)
10. dry with materialThe organic layer was dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure

ORD record

ord-c3b719c3ed9c4ec89331bebedfe9b317

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822456B2