Diethyl Malonate → Diethyl 2-(2-(3-chlorophenyl)-2-methylpropanoyl)malonate

Temperature

0 °C

Diethyl malonate (3.72 mL, 24.6 mmol) in ACN (50 mL) was cooled to 0° C. MgCl2 (2.34 g, 24.6 mmol) was added, followed by addition of TEA (7.18 mL, 51.7 mmol) slowly via syringe. The mixture was stirred at 0° C. for 15 minutes before being brought to room temperature and stirred for 2.5 hours. 2-(3-Chlorophenyl)-2-methylpropanoyl chloride (5.69 g, 24.6 mmol) was dissolved in ACN (20 mL) and added to the malonate solution. The reaction mixture was then stirred at 50° C. for 16 hours. The reaction mixture was cooled to room temperature, concentrated in vacuo, and partitioned between 1M HCl and EtOAc. The aqueous layer was separated and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4) and concentrated in vacuo to give the desired compound as a brown oil (8.76 g). MS (m/e)=341.2 (M+H)+.

1. custombefore being brought to room temperature
2. stirringstirred for 2.5 hours
3. stirringThe reaction mixture was then stirred at 50° C. for 16 hours
4. temperatureThe reaction mixture was cooled to room temperature
5. concentrationconcentrated in vacuo
6. custompartitioned between 1M HCl and EtOAc
7. customThe aqueous layer was separated
8. extractionextracted with EtOAc (2×)
9. dry with materialThe combined organic layers were dried (MgSO4)
10. concentrationconcentrated in vacuo

ORD record

ord-1c1ea7da36254fb4a25ae13257dae70a

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07635715B2