Boron trifluoride etherate → Ethyl 5-(1-hydroxybut-3-en-1-yl)-4-methylisoxazole-3-carboxylate

Temperature

-78 °C

To a solution of ethyl 5-formyl-4-methylisoxazole-3-carboxylate (Intermediate C) (350 mg, 1.911 mmol) in DCM (19 mL) was added allyltrimethylsilane (276 μl, 1.911 mmol) and the mixture was cooled to −78° C. A solution of boron trifluoride etherate (278 μl, 2.198 mmol) in DCM (5 mL) was cooled to −78° C. and added to the reaction mixture over 5 min. The reaction mixture was stirred for 15 mins and triethylamine (266 μl, 1.911 mmol) was added. The reaction mixture was maintained at −78° C. for 15 minutes and allowed to warm to room temperature. The resulting mixture was quenched by the addition of a saturated aqueous NaHCO3 solution (10 mL) and extracted with DCM (2×10 mL). The combined organic extracts were passed through a phase separating cartridge and the solvent removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-40% EtOAc in iso-hexane afforded the title compound;

1. additionadded to the reaction mixture over 5 min
2. temperatureThe reaction mixture was maintained at −78° C. for 15 minutes
3. temperatureto warm to room temperature
4. customThe resulting mixture was quenched by the addition of a saturated aqueous NaHCO3 solution (10 mL)
5. extractionextracted with DCM (2×10 mL)
6. customseparating cartridge
7. customthe solvent removed under reduced pressure
8. customThe crude material was adsorbed onto silica and purification by chromatography
9. washeluting with 0-40% EtOAc in iso-hexane

ORD record

ord-90cc26303780486e91700b0d8fb6e925

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403810B2