Patent ID: 6790964
Filing Date: 2004-09-14
Classification: C07C,C07D

Abstract:
A production method of a 7-azabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ester of the formula (VII) wherein R1 is an alkyl group optionally having substituents, a cycloalkyl group optionally having substituents, an aryl group optionally having substituents or an aralkyl group optionally having substituents and R3 is an alkyl group optionally having substituents, a cycloalkyl group optionally having substituents, an alkenyl group optionally having substituents, an aryl group optionally having substituents or an aralkyl group optionally having substituents, which comprises the steps of(A) reacting a 5-hydroxy-7-oxabicyclo[4.1.0]hept-2-ene-3-carboxylic acid ester of the formula (I) wherein R1 is as defined above, with an amine of the formula (II)R2NH2â€ƒâ€ƒ(II) wherein R2 is a hydrogen atom, an alkyl group optionally having substituents, a cycloalkyl group optionally having substituents, an alkenyl group optionally having substituents, an aryl group optionally having substituents or an aralkyl group optionally having substituents, to give a 3-amino-4,5-dihydroxy-1-cyclohexene-1-carboxylic acid ester of the formula (III) wherein R1 and R2 are as defined above,(B) reacting the obtained 3-amino-4,5-dihydroxy-1-cyclohexene-1-carboxylic acid ester with a sulfonylating agent in the presence of a base to give a 5-sulfonyloxy-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylic acid ester of the formula (IV) wherein R1 and R2 are as defined above and A is an organic sulfonyl group,(C) reacting the obtained 5-sulfonyloxy-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylic acid ester with an alcohol of the formula (V) R3OHâ€ƒâ€ƒ(V) wherein R3 is as defined above, in the presence of a Lewis acid to give a 5-oxy-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ester of the formula (VI) wherein R1, R2 and R3 are as defined above, and(D) when R2 is an alkyl group optionally having substituents, a cycloalkyl group optionally having substituents, an alkenyl group optionally having substituents, an aryl group optionally having substituents or an aralkyl group optionally having substituents, eliminating the 7-position substituent R2 of the obtained 5-oxy-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ester.