Thionyl Chloride → Ethyl 7-hydroxy-3-(thiophen-2-yl)isoxazolo[4,5-c]pyridine-6-carboxylate

Temperature

-78 °C

Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(thiophen-2-yl)isoxazole-5-carboxylate (2.2 g, 4.51 mmol) was dissolved in 40 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (9 mL, 9.02 mmol, 1M in THF) was added dropwise, and the mixture was stirred for 14 hours, the cold bath allowed to evaporate spontaneously. The reaction mixture was quenched with 8 mL of 1M HCl and 50 mL of saturated ammonium chloride solution. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 2.0 g of crude oil. The crude intermediate was dissolved in 25 mL of CH2Cl2. Thionyl chloride (0.49 mL, 6.79 mmol) was added and the reaction mixture was stirred for 3 h. The mixture was filtered through a medium porosity funnel. The solid was rinsed three times with cold CH2Cl2 and dried under vacuum to give 0.88 g of the title compound. MS: (+) m/z 291.34 (M+1).

1. customto evaporate spontaneously
2. customThe reaction mixture was quenched with 8 mL of 1M HCl and 50 mL of saturated ammonium chloride solution
3. extractionThe product was extracted with EtOAc
4. dry with materialthe organic layer was dried over MgSO4
5. concentrationconcentrated
6. customto give 2.0 g of crude oil
7. stirringthe reaction mixture was stirred for 3 h
8. filtrationThe mixture was filtered through a medium porosity funnel
9. washThe solid was rinsed three times with cold CH2Cl2
10. customdried under vacuum

ORD record

ord-98efe303f170410cab3262bf45ce3908

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08269008B2