Isobutyric Acid → 2,2-Dimethyl-3-phenylpropanoic acid

Temperature

0 °C

To a mixture of 1.23 g (41.0 mmol) of 80% sodium hydride and 50 mL of anhydrous tetrahydrofuran under a nitrogen atmosphere, was added 3.88 g (38.3 mmol) of diisopropylamine and then 3.3 g (37.5 mmol) of isobutyric acid. After heating at reflux for 15 minutes and cooling to 0° C., 15 mL (37.5 mmol) of 2.5M n-butyllithium in hexane was added. The mixture was warmed to 35° C. for 30 min, cooled to 0° C. and 6.40 g (37.5 mmol) of benzyl bromide added. The mixture was stirred for 30 minutes at 0° C., then warmed to 35° C. for one hour and recooled to 0° C. Water was added and the aqueous layer extracted with diethyl ether, acidified with 6N aqueous HCl and extracted with diethyl ether. The organic layer was dried and concentrated to provide 4.0 g of crude product. Chromatography on silica gel using 10% methanol/methylene chloride afforded 1.0 g of pure 2,2-dimethyl-3-phenylpropionic acid, m/e 185 (M+Li).

1. temperatureAfter heating
2. temperatureat reflux for 15 minutes
3. temperatureThe mixture was warmed to 35° C. for 30 min
4. temperaturecooled to 0° C.
5. temperaturewarmed to 35° C. for one hour
6. customrecooled to 0° C
7. extractionthe aqueous layer extracted with diethyl ether
8. extractionextracted with diethyl ether
9. customThe organic layer was dried
10. concentrationconcentrated
11. customto provide 4.0 g of crude product

ORD record

ord-7861b1942502491588883b3edd3aae3b

Source dataset

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05614522