Methanol → Ethyl 4-methoxy-3-oxobutanoate

A mixture of 15.8 g of ethyl 4-chloroacetoacetate (96.2 mmol) and 3.39 g of methanol (106 mmol) in 10 mL of THF were added dropwise to a stirred suspension of 4.62 g of 60% NaH (in mineral oil), 1.60 g of NaI (9.62 mmol), and 3.10 g of tetrabutylammonium bromide (9.62 mmol) in 40 mL of THF at -30° C. over a period of 1.5 hrs. The reaction mixture was then warmed to room temperature and stirred for 4 days. The reaction mixture was cooled to -30° C., quenched with 5 mL of methanol, and warmed to room temperature. The reaction mixture was poured into 0.5 L of 10% HCl solution, extracted with 2×100 mL of EtOAc, dried (Na2 SO4), and the solvent was removed in vacuo. The crude product was distilled. The fraction boiling at 65°-70° C. (0.3 mm Hg) was collected and used in the next experiments after spectral characterization.

1. temperatureThe reaction mixture was cooled to -30° C.
2. customquenched with 5 mL of methanol
3. temperaturewarmed to room temperature
4. additionThe reaction mixture was poured into 0.5 L of 10% HCl solution
5. extractionextracted with 2×100 mL of EtOAc
6. customdried (Na2 SO4)
7. customthe solvent was removed in vacuo
8. distillationThe crude product was distilled
9. customThe fraction boiling at 65°-70° C. (0.3 mm Hg) was collected

ORD record

ord-5d01b57dff1947d7b3e9b60465c36697

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05767131