Diethyl Malonate → Diethyl 2-(2-(4-fluorophenyl)-2-methylpropanoyl)malonate

Temperature

0 °C

A mixture of diethyl malonate (3 g, 16 mmol) in 50 mL ACN was stirred at 0° C., was treated with MgCl2 (2 g, 18 mmol) in one portion, and was treated dropwise with TEA (3 g, 33 mmol). The mixture was stirred at room temperature for 2.5 hours. A mixture of 2-(4-fluorophenyl)-2-methylpropanoic acid (3 g, 16 mmol) in thionyl chloride (20 mL) was refluxed for 2 hours and then concentrated in vacuo. The residue was diluted with 10 mL ACN, and was added dropwise to the above mixture. The mixture was stirred at 50° C. for 15 hours. The resulting mixture was then cooled to room temperature, diluted with 100 mL ether, washed with H2O (2×50 mL) and brine 20 mL, dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was purified by column chromatography eluting with 10-20% EtOAc/hexane to give 5 g of the product as pale yellow oil. MS m/e=325 (M+H)+.

1. stirringThe mixture was stirred at room temperature for 2.5 hours
2. temperaturewas refluxed for 2 hours
3. concentrationconcentrated in vacuo
4. additionThe residue was diluted with 10 mL ACN
5. additionwas added dropwise to the above mixture
6. stirringThe mixture was stirred at 50° C. for 15 hours
7. temperatureThe resulting mixture was then cooled to room temperature
8. additiondiluted with 100 mL ether
9. washwashed with H2O (2×50 mL) and brine 20 mL
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated in vacuo
12. customThe crude product was purified by column chromatography
13. washeluting with 10-20% EtOAc/hexane

ORD record

ord-18c0cb6cc0984bc99a5effa35e620067

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928139B2