Nicotinic Acid → 2-Chloronicotinic acid

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Reaction Steps

Alternatively, the intermediate 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester, depicted by formula 37 in Scheme 15 can be prepared from 4-chloro pyridine or nicotinic acid as shown in Scheme 16. Ortholithiation of 4-chloropyridine by LDA followed by quenching with dry ice or lithiation of nicotinic acid followed by quenching with hexachloroethane can give chloronicotinic acid intermediate, depicted by formula 39 in Scheme 16. Amination of this intermediate can give 3-(4-methoxy-benzylamino)-nicotinic acid, depicted by formula 40 in Scheme 16, which was converted to 1-(4-methoxy-benzyl)-1H-pyrido[4,3-d][1,3]oxazine-2,4-dione depicted by formula 41 in Scheme 16, by treating with trichloromethyl chloroformate. This intermediate can be converted into 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester, depicted by formula 37 in Scheme 15, as shown in Scheme 16.

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