Hydrochloric Acid → Pentanenitrile, 4,4-dimethyl-3-oxo-

Participants

Reaction Conditions

Reaction Steps

Cyanoacetic acid (8.5 g) was dissolved in dry THF (300 ml), placed under an inert atmosphere and the solution cooled using a dry ice-acetone bath. Butyllithium (80 ml of a 2.5M solution in hexane) was added dropwise over 1 hour. During the addition the internal reaction temperature was maintained below -65° C. The reaction mixture was stirred in the dry ice-acetone bath for 1 hour and then the bath was removed and the reaction stirred for an additional hour, during which time the internal temperature rose to -45° C. The resultant reaction mixture was cooled to -70° C. and trimethylacetyl chloride (6.0 g) in THF (50 ml) added dropwise over 30 minutes while keeping the temperature of the reaction mixture below -65° C. The reaction mixture was allowed to stir in a dry ice-acetone bath for 1 hour and then allowed to warm to room temperature overnight. The resultant mixture was acidified by the addition of 2N HCl (200 ml) and diluted with CH2Cl2 (500 ml). The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (MgSO4) and, after removal of the drying agent by filtration, the solvents were removed. The residue was dissolved in ether (200 ml) and the etheral solution extracted with 2N NaOH (twice with 50 ml portions). To the combined aqueous extracts was added conc. HCl to adjust the solution to pH 1. The resulting mixture was extracted with ether. The combined extracts were dried (MgSO4) and, after removal of the drying agent by filtration, the solvents were removed to afford 5.6 g of 4,4-dimethyl-3-oxopentanonitrile as an orange oil which slowly solidified; m.p. 60° C.

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