HCID 11124297, compound → HCID 69820135, compound

Temperature

-78 °C

To tetrahydrofuran (30 mL) was added (6-bromo-4-ethyl-benzo[1,3]dioxole) (1.24 g, 5.41 mmol). After cooling to −78° C., a solution of n-butyllithium (1.6 M in hexane, 3.54 mL) was added. After stirring for 45 minutes, a solution of anhydrous zinc bromide (1.27 g, 5.69 mmol) in tetrahydrofuran (20 mL) was added, and the mixture was stirred at −72° C. for 45 minutes, followed by warming to −25° C. To this mixture was added 1,1-dioxo-4-(trifluoro-methanesulfonyloxy)-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester (1.49 g, 2.80 mmol), and palladium tetrakis(triphenyl phosphine) (1.30 g, 1.05 mmol). The mixture was heated to 70° C. for 2.5 hours and was evaporated in vacuo to an oil. The mixture was resuspended in ethyl acetate, washed with 1N citric acid solution, brine, filtered, and dried over anhydrous magnesium sulfate. The suspension was filtered and stripped to an oil which was partially crystallized from ethyl ether giving a solid. The filtrate was concentrated in vacuo and was chromatographed on 50 g silica gel eluted with a mixture of ethyl acetate and hexane (30:70). The appropriate fractions were concentrated in vacuo and crystallized from ethyl ether. These solids were combined with those recovered from the initial crystallization and were dried in vacuo giving a solid, 0.836 g, 53% yield. NMR spectra and elemental analysis were consistent with the structure.

1. stirringthe mixture was stirred at −72° C. for 45 minutes
2. temperatureby warming to −25° C
3. temperatureThe mixture was heated to 70° C. for 2.5 hours
4. customwas evaporated in vacuo to an oil
5. washwashed with 1N citric acid solution, brine
6. filtrationfiltered
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationThe suspension was filtered
9. customwas partially crystallized from ethyl ether giving a solid
10. concentrationThe filtrate was concentrated in vacuo
11. customwas chromatographed on 50 g silica gel
12. washeluted with a mixture of ethyl acetate and hexane (30:70)
13. concentrationThe appropriate fractions were concentrated in vacuo
14. customcrystallized from ethyl ether
15. customthose recovered from the initial
16. customcrystallization
17. customwere dried in vacuo
18. customgiving a solid, 0.836 g, 53% yield

ORD record

ord-b67af67da376483b8eee77aa69c5767e

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06265399B1