Acetic Acid → 3-(trifluoromethyl)pentanedioic Acid

Temperature

40 °C

To 115 mg (5 mmol) of sodium metal (cut into small pieces and washed with hexanes) in 5 ml of THF was added a solution of diethyl malonate (800 mg, 5 mmol) in 10 ml THF. The mixture was stirred at room temperature until all of the sodium metal was consumed (2-3 hours). A catalytic amount of tetrabutylammonium bromide was added, followed by a THF solution (10 ml) of ethyl 4,4,4-trifluorocrotonate (0.84 g, 5 mmol). This mixture was-warmed to 40° C. and stirred for 17 hours. After cooling to 10° C., glacial acetic acid (300 mg, 5 mmol) was added and the THF was removed in vacuo. The resulting residue was treated with a solution of 87.3% KOH (1.28 g, 20 mmol) in 10 ml water and refluxed for 4.5 hours. After cooling to 10° C., 2.5 ml (26 mmol) of conc. HCl was added dropwise via pipette and the mixture was again heated to reflux until CO2 evolution had ceased (ca. 1 hour). The solution was cooled to 15° C. and extracted with Et2O (3×10 ml). The combined organic phases were dried over Na2SO4 , filtered and concentrated in vacuo to afford 3-(trifluoromethyl)glutaric acid as a white solid in 95% yield (m.p. 100°-100.5° C.).

1. customwas consumed (2-3 hours)
2. additionA catalytic amount of tetrabutylammonium bromide was added
3. temperatureAfter cooling to 10° C.
4. customthe THF was removed in vacuo
5. temperaturerefluxed for 4.5 hours
6. temperatureAfter cooling to 10° C.
7. temperaturethe mixture was again heated
8. custom(ca. 1 hour)
9. temperatureThe solution was cooled to 15° C.
10. extractionextracted with Et2O (3×10 ml)
11. dry with materialThe combined organic phases were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-a4fd3a1bed5740e39f3bec2158ea40c6

Source dataset

uspto-grants-1995_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05393735