Hydrochloric Acid → 5-Methoxy-4,4-dimethyl-3-oxopentanenitrile

A solution of 1.74 g (12 mmol) of 3-methoxy-2,2-dimethyl-propionic acid methyl ester and 0.9 mL (17 mmol) of acetonitrile in toluene (5 mL) is added dropwise to the refluxing suspension of 0.67 g (17 mmol) of sodium hydride (60% in mineral oil) in toluene (5 mL). After the addition, the reaction mixture is stirred at reflux for 3 h. After this time, the reaction mixture is cooled to room temperature and neutralized to pH ˜6-7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate (3×20 mL). The organic layers are combined, washed with brine (1.5 L), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield 1.69 g of 5-methoxy-4,4-dimethyl-3-oxo-pentanenitrile as a brown oil, which is used in the next step without further purification. Yield: 91%; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.1 (6H, s), 3.2 (3H, s), 3.3 (2H, s), 4.2 (2H, s).

1. additionAfter the addition
2. temperatureat reflux for 3 h
3. extractionThe aqueous layer is extracted with ethyl acetate (3×20 mL)
4. washwashed with brine (1.5 L)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationThe filtrate is concentrated under reduced pressure

ORD record

ord-f8c82b1ac7b540ecad3df37d15bad9fc

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349871B2