反应详情

A mixture of methyl (R)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzene-sulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 1, 0.640 g) and lithium hydroxide monohydrate (0.505 g) in dioxane (9.6 mL) and water (2.4 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was acidified with formic acid, diluted with ethanol and toluene and concentrated in vacuo. The residue was triturated with methanol in DCM (10% solution) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-10%. The resultant solid was triturated with ethyl acetate to give a pale yellow solid which was treated with hot ethyl acetate and filtered while still hot. The filtrate was concentrated in vacuo and the residue was triturated with ethyl acetate to give (R)-7-[2-((Z)-3-diethylaminoprop-1-en-1-yl)-4-fluorobenzenesulfonyl-amino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acid (0.299 g) as a pale yellow solid.

1. customwas irradiated in the microwave at 135° C. for 45 minutes
2. temperatureAfter cooling
3. concentrationconcentrated in vacuo
4. customThe residue was triturated with methanol in DCM (10% solution)
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customthe residue was purified by chromatography on silica
8. washeluting with a mixture of methanol and DCM with a gradient of 0-10%
9. customThe resultant solid was triturated with ethyl acetate
10. customto give a pale yellow solid which
11. filtrationfiltered while still hot
12. concentrationThe filtrate was concentrated in vacuo
13. customthe residue was triturated with ethyl acetate