Sodium hydride → 2-(3,3-Diethoxypropyl)-2-(3,4-dimethoxyphenyl)acetonitrile

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Reaction Steps

An optionally substituted phenyacetonitrile or lower alkyl phenylacetic ester is then alkylated with an ω-halopropionaldehyde acetal using a strong metallic base in polar, aprotic solvent. The desired phenylacetonitrile derivative or lower alkyl phenylacetic ester derivative is first deprotonated by adding about 1 eq of a strong metallic base, e.g., NaH, in a polar aprotic solvent at 15°-21° C. over 25-50 minutes. The resulting mixture is then stirred for 1-3 hours, and about 1 eq of 3-chloropropionaldehyde diethylacetal is added to yield a derivative of formula 5 (step 3). For example, 2-(3,4-dimethoxyphenyl)acetonitrile in dimethyl formamide (DMF) is added to NaH at 18°-20° C. over a 30 minute period, stirred for one hour, and then treated with 3-chloropropionaldehyde diethylacetal in DMF to yield 2-(3,3-diethoxypropyl)-2-(3,4-dimethoxyphenyl)acetonitrile (5).

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