Sodium Hydroxide → N-(3-((4aS,7aS)-2-Benzamido-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

Temperature

22 °C

A mixture of N-((4aS,7aS)-7a-(5-amino-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (20.4 g, 51.8 mmol), 5-fluoropicolinic acid (8.77 g, 62.2 mmol), 1-hydroxybenzotriazole hydrate (10.3 g, 67.4 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (13.2 g, 67.4 mmol) in a mixture of dichloromethane (345 mL) and DMF (6.5 mL) is stirred at 22° C. for 80 min. A solution of 2 M sodium hydroxide (129.5 mL, 259 mmol) is added and the stirring is continued for 10 min. The mixture is separated and the aqueous phase is extracted with twice with dichloromethane (2×100 mL). The organic layer is concentrated under reduced pressure and the residue is diluted with ethyl acetate (200 mL). The organic layer is washed with cooled water (2×50 mL), brine (50 mL) and filtered through a short pad of silica using 100% ethyl acetate to give title compound (23.8 g, 79%). ES/MS m/e: 495 (M+1).

1. waitthe stirring is continued for 10 min
2. customThe mixture is separated
3. extractionthe aqueous phase is extracted with twice with dichloromethane (2×100 mL)
4. concentrationThe organic layer is concentrated under reduced pressure
5. additionthe residue is diluted with ethyl acetate (200 mL)
6. washThe organic layer is washed with cooled water (2×50 mL), brine (50 mL)
7. filtrationfiltered through a short pad of silica using 100% ethyl acetate

ORD record

ord-7be03ea75b8a40eea2e6b40e20564cb8

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278441B2