Diethyl Malonate → HCID 67099639, compound

Temperature

25 °C

A solution of 2-(4-chloro-3-fluorophenyl)-2-methylpropanoic acid (2.05 g, 9.46 mmol) in thionyl chloride (40.0 mL, 548 mmol) in a 500 mL round bottom flask was stirred at 95° C. for 2 hours. The reaction was concentrated in vacuo and azeotroped in toluene (50 mL) to give the crude acid chloride. A solution of diethyl malonate (1.43 mL, 9.46 mmol) in ACN (20 mL) was cooled to 0° C. MgCl2 (0.901 g, 9.46 mmol) and then TEA (2.76 mL, 19.9 mmol) were added, and the mixture was stirred at 25° C. for 2 hours. A solution of the acid chloride in ACN (30 mL) was added, and the mixture was stirred at 50° C. for 16 hours. The reaction was cooled, diluted with water (75 mL), and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (75 mL) and brine (75 mL). The organic layer was dried over MgSO4, concentrated, and dried in vacuo to give diethyl 2-(2-(4-chloro-3-fluorophenyl)-2-methylpropanoyl)malonate (2.95 g). MS m/e=359.4 (M+H)+.

1. concentrationThe reaction was concentrated in vacuo
2. customazeotroped in toluene (50 mL)
3. customto give the crude acid chloride
4. stirringthe mixture was stirred at 50° C. for 16 hours
5. temperatureThe reaction was cooled
6. extractionextracted with EtOAc (2×100 mL)
7. washThe combined organic layers were washed with water (75 mL) and brine (75 mL)
8. dry with materialThe organic layer was dried over MgSO4
9. concentrationconcentrated
10. customdried in vacuo

ORD record

ord-b5b96364249c4ebebc3448415cada714

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07635715B2