A convenient synthesis of 1‐methyl‐4‐oxopiṕecolic acid methyl ester

Abstract

An efficient and convenient synthesis of the title compond 1 is described. The approach to the synthesis is based on hydride reduction of the 4‐methoxypyridinium salt 5, followed by acid hydrolysis of the resulting vinyl ether intermediate 6.

Partial Reduction of Pyridinium Salts as a Versatile Route to Dihydropyridones

“…We undertook an efficient, one-pot, synthesis of activated pyridine 5 from picolinic acid (Scheme ) . Subsequent N-alkylation was achieved in excellent yield to furnish pyridinium salts 6 and 7 . The rationale behind the addition of a methoxy group at C-4 was to avoid the generation of an unstable 1,2-dihydropyridine after reduction: acid-catalyzed hydrolysis in situ was predicted to liberate a dihydropyridone that would be straightforward to handle.…”

“…The dihydropyridones ( 11 − 14 ) were furnished in good yield using a range of electrophiles. We were pleased to find that the methodology was applicable to electrophiles, such as methyl chloroformate, that cannot be used under the standard Birch reduction conditions (entry 8, Scheme ) . Thus we have defined a highly versatile method for introducing groups α to the nitrogen with great potential for broader synthetic application.…”