Triethylamine → Ethyl 5-bromo-4-methyl-1,2-oxazole-3-carboxylate

Temperature

80 °C

Ethyl 4-methyl-5-oxo-4,5-dihydroisoxazole-3-carboxylate (42.5 g, 248 mmol) and phosphorous oxybromide (199 g, 695 mmol) were stirred together and heated to 80° C. Triethylamine (34.6 mL, 248 mmol) was added dropwise over 15 mins and the reaction mixture was stirred at 80° C. for 3 hours. The resulting mixture was cooled to room temperature. DCM (400 mL) was added and the mixture was poured into ice (˜400 mL) with stirring. 2M NaOH (aq) (1250 mL) was added until pH 7 and the resulting layers were separated. The aqueous layer was extracted with DCM (2×300 mL) and the resulting organic extracts were combined, washed with water (400 mL), sodium thiosulfate (5% w/v solution, 400 mL), water (400 mL) and brine (400 mL). The organics were dried over MgSO4 and charcoal, filtered and the solvent removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-30% EtOAc in iso-hexane afforded the title compound;

1. temperatureThe resulting mixture was cooled to room temperature
2. stirringwith stirring
3. customthe resulting layers were separated
4. extractionThe aqueous layer was extracted with DCM (2×300 mL)
5. washwashed with water (400 mL), sodium thiosulfate (5% w/v solution, 400 mL), water (400 mL) and brine (400 mL)
6. dry with materialThe organics were dried over MgSO4 and charcoal
7. filtrationfiltered
8. customthe solvent removed under reduced pressure
9. customThe crude material was adsorbed onto silica and purification by chromatography
10. washeluting with 0-30% EtOAc in iso-hexane

ORD record

ord-539abb6ec4de43898c2dd5e066dcb85d

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403810B2