alpha-Methylbutyrolactone → 4-Hydroxy-1-(2-chloro-4-methoxyphenyl)-2-methylbutan-1-one

Temperature

-85 °C

To a 1.0 L, 3-neck round bottom flask, equipped with a mechanical stirrer and an internal thermometer, was added a solution of 4-bromo-3-chloroanisole (12.0 g, 54.0 mmol) in 350 mL of THF under nitrogen. The solution was cooled to −85° C. with a MeOH/liquid nitrogen bath. To this solution was added t-BuLi (72.0 mL, 1.6 M in pentane, 122 mmol) slowly followed by the addition of a solution of α-methyl-γ-butyrolactone (9.25 g, 92.0 mmol) in THF (30.0 mL). The internal temperature was controlled <−80° C. After 1 h stirring at <−80° C., the reaction mixture was quenched with saturated NH4Cl solution and warmed to room temperature. Water and EtOAc were added and separated. The aqueous layer was extracted with EtOAc (2×). The combined organic solutions was dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (E:H, 1:3) to give 10.4 g (79%) of brown oil as the title compound: 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J=8.6 Hz, 1H), 6.97 (d, J=2.4 Hz, 1H), 6.85 (dd, J=8.6, 2.4 Hz, 1H), 3.88 (s, 3H), 3.77–3.69 (m, 2H), 3.64–3.56 (m, 1H), 2.16–2.07 (m, 1H), 1.76–1.67 (m, 1H), 1.23 (d, J=7.0 Hz, 3H); MS (EI m/z 241.16 (M+−H).

1. customTo a 1.0 L, 3-neck round bottom flask, equipped with a mechanical stirrer
2. customwas controlled <−80° C
3. customthe reaction mixture was quenched with saturated NH4Cl solution
4. temperaturewarmed to room temperature
5. additionWater and EtOAc were added
6. customseparated
7. extractionThe aqueous layer was extracted with EtOAc (2×)
8. dry with materialThe combined organic solutions was dried (MgSO4)
9. filtrationfiltered
10. concentrationThe filtrate was concentrated in vacuo to dryness

ORD record

ord-d439d44ef0e745b3baa7be0c35be55ba

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07056920B2