Lithium Hydroxide → HCID 86762248, compound

To N-[(4aR,7aR)-6-(5-fluoropyrimidin-2-yl)7a-(5-fluorothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (391 mg, 855 mmol) is added methanol (8.5 mL) and lithium hydroxide (179 mg, 4.27 mmol). The solution is heated to reflux for 2.5 hours under an atmosphere of nitrogen. The resulting solution is allowed to cool for a few minutes then concentrated under reduced pressure. The residue is extracted with dichloromethane (30 mL) and water (30 mL). The phases are partitioned and the aqueous phase further extracted with dichloromethane (1×30 mL). The combined dichloromethane extracts are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with dichloromethane/methanol, gradient from 99:1 to 90:10, to give the title compound (263 mg, 87%) as an amorphous white foam. ES/MS (m/e): 354.0 (M+H).

1. temperatureThe solution is heated
2. temperatureto reflux for 2.5 hours under an atmosphere of nitrogen
3. temperatureto cool for a few minutes
4. concentrationthen concentrated under reduced pressure
5. extractionThe residue is extracted with dichloromethane (30 mL) and water (30 mL)
6. customThe phases are partitioned
7. extractionthe aqueous phase further extracted with dichloromethane (1×30 mL)
8. dry with materialThe combined dichloromethane extracts are dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue is purified by silica gel chromatography
12. washeluting with dichloromethane/methanol, gradient from 99:1 to 90:10

ORD record

ord-c50f149efd5c42688ec47ec2c55b9f3c

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772282B2