diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-

Uses

Dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate is a useful intermediate for the preparation of dolutegravir and dolutegravir salts used in antiretroviral medications.

Synthesis

To a reaction flask was added 30 mmol of methyl 4-benzyloxy-2-((dimethylamino)methylene)-3-acetoacetate (product of Example 2), 45 mmol of dimethyl oxalate, 15 mmol of sodium tert-butanol and 300 mL of toluene. The reaction flask was placed in an oil bath, heated to 105 °C and refluxed for 6 hours. After the reaction was completed, it was cooled to room temperature and filtered. The toluene solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography with the eluent hexane:ethyl acetate=9:4 (v/v) to afford dimethyl 4-oxo-3-benzyloxy-4H-pyran-2,5-dicarboxylate in 90% yield.

References

[1] Patent: CN108101838, 2018, A. Location in patent: Paragraph 0038; 0039; 0040; 0041
[2] Patent: US2012/22251, 2012, A1. Location in patent: Page/Page column 24-25
[3] Patent: EP2602260, 2013, A1. Location in patent: Paragraph 0124