Process for the preparation of...

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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Reexamination Certificate

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06963002

ABSTRACT:
An improved process for the preparation of key intermediates for tazarotene, 4,4-dimethyl-6-ethynylthiochroman, is provided comprising (a) reacting 4,4-dimethyl-6-acetylthiochroman of the formulawith an acid chloride and an amido-group containing compound of the general formulawherein R is hydrogen or a hydrocarbyl of from 1 to 15 carbon atoms and R1and R2can be the same or different and are hydrocarbyls of from 1 to 15 carbon atoms or R1and R2together with the nitrogen atom to which they are bonded are joined together to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms, or one of R1and R2together with the nitrogen atom to which it bonded are joined together with the carbonyl radical to form a heterocyclic group, optionally containing one or more additional heterocyclic atoms to form a β-chloro vinyl carbonyl compound intermediate of the general formulawherein R has the aforestated meanings; and (b) reacting the β-chloro vinyl carbonyl compound intermediate with an alkali metal to provide the 4,4-dimethyl-6-ethynylthiochroman.

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Johnson et al. “Synthesis and Biological Activity of High-Affininty Retinoic Acid Receptor Antagonists”, Bioorganic & MedicinalChemistry, Elsevier Science Ltd., (7):1321-1338, Jul. 1999.

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