Baylis-Hillman Route to Several Quinolone Antibiotic Intermediates

Abstract

Treatment of methyl propiolate and 2,4,5-trifluoro-, 2-fluoro-, 2-fluoro-5-methoxy- or 2,3,4,5-tetrafluorobenzaldehydes with a ZrCl₄/Bu₄NI combination induces an aldol reaction to furnish β-iodo-α-(hydroxyalkyl)acrylates. These can be used for the preparation of several quinolone intermediates, 1-substituted 4-oxo-1,4-dihydroquinoline-3-carboxylic acids and 9,10-difluoro-3-methyl-2,3-dihydro-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbox­ylic acid through the oxidation, amination and hydrolysis reactions.

Key words

Baylis-Hillman reaction - quinolone antibiotics - β-iodo-α-(hydroxyalkyl)acrylates - Dess-Martin periodinane - α-methylene-β-keto ester

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18

In references 10 and 6c, the overall yields of 6a (48%) and 12 (30%) were reported from the corresponding benzoyl chlorides, respectively.