Benzyl Chloride → 3-Benzyloxy-2-methyl-4-pyrone

To a suspension of maltol (126 g, 1.0 mol) and methanol (450 mL) in a 2 L 3-necked round bottom flask equipped with a mechanical stirrer was added a 10.0 N sodium hydroxide solution (110 mL, 1.1 mol). A clear solution resulted upon stirring. Benzyl chloride (138 mL, 1.2 mol) was then added, and the resulting solution was heated to reflux for 1.5 h. To the reaction mixture was further added a 10.0 N sodium hydroxide (20 mL, 0.2 mol) and benzyl chloride (27 mL, 0.23 mol), and the reaction mixture was heated to reflux for another 2 h. The progress of the reaction was monitored by HPLC Method 4 (Example 24), and the amount of remaining unreacted maltol was about 2%. The reaction mixture was stirred overnight. The mixture was cooled to RT and filtered. The filtrate was concentrated in vacuo to a volume of about 300 mL, as two phases could be observed. The top layer was collected via separatory funnel, and was concentrated under reduced pressure to give 3-(benzyloxy)-2-methyl-4H-pyran-4-one as an oil (220 g, 95% yield, HPLC Method 4 (Example 24), RT=15.5 min, HPLC purity (peak percent area): 95% at λ=280 nm). 1H NMR (DMSO-d6) δ ppm: 8.04 (d, J=5.5 Hz, 1H), 7.37, (m, 5H), 6.37 (d, J=5.5 Hz, 1H), 5.02 (s, 2H), 2.12 (s, 3H).

1. customequipped with a mechanical stirrer
2. customA clear solution resulted
3. temperaturethe resulting solution was heated
4. temperatureto reflux for 1.5 h
5. temperaturethe reaction mixture was heated
6. temperatureto reflux for another 2 h
7. stirringThe reaction mixture was stirred overnight
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo to a volume of about 300 mL, as two phases
10. customThe top layer was collected via separatory funnel
11. concentrationwas concentrated under reduced pressure

ORD record

ord-43c3615b9b5c4f18bf64c9a12152af8d

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673943B2