The intermediate gamma-sultam (III) was prepared by condensation of 3-chloropropylsulfonyl chloride (I) with ethylamine, followed by cyclization of the resulting chloro sulfonamide (II) under basic conditions. Condensation of 3,5-di-tert-butyl-4-(methoxymethoxy)benzaldehyde (IV) with sultam (III) in the presence of LDA produced the aldol addition compound (V). Then, acid-promoted dehydration and simultaneous methoxymethyl group deprotection gave rise to a mixture of the desired E-benzylidene sultam and the corresponding Z-isomer (VII), which were separated by column chromatography.

An improved synthesis has been reported. Acid-catalyzed ketalization of aldehyde (VIII) with trimethyl orthoformate provided the dimethyl acetal (IX) which, upon thermal decomposition in refluxing xylene, gave rise to the alpha-methoxy methylenequinone derivative (X). This was then condensed with the lithio derivative of sultam (III) to form selectively the desired E-adduct. In an analogous procedure, aldehyde (VIII) was converted to the chloromethylene compound (XI) with methanesulfonyl chloride and triethylamine in refluxing CH2Cl2. Condensation of (XI) with the lithiated sultam (III) furnished the desired E-benzylidene sultam.

The intermediate gamma-sultam (III) was prepared by condensation of 3-chloropropylsulfonyl chloride (I) with ethylamine, followed by cyclization of the resulting chloro sulfonamide (II) under basic conditions. Condensation of 3,5-di-tert-butyl-4-(methoxymethoxy)benzaldehyde (IV) with sultam (III) in the presence of LDA produced the aldol addition compound (V). Then, acid-promoted dehydration and simultaneous methoxymethyl group deprotection gave rise to a mixture of the desired E-benzylidene sultam and the corresponding Z-isomer (VII), which were separated by column chromatography.

The intermediate gamma-sultam (III) was prepared by condensation of 3-chloropropylsulfonyl chloride (I) with ethylamine, followed by cyclization of the resulting chloro sulfonamide (II) under basic conditions. Condensation of 3,5-di-tert-butyl-4-(methoxymethoxy)benzaldehyde (IV) with sultam (III) in the presence of LDA produced the aldol addition compound (V). Then, acid-promoted dehydration and simultaneous methoxymethyl group deprotection gave rise to a mixture of the desired E-benzylidene sultam and the corresponding Z-isomer (VII), which were separated by column chromatography.

An improved synthesis has been reported. Acid-catalyzed ketalization of aldehyde (VIII) with trimethyl orthoformate provided the dimethyl acetal (IX) which, upon thermal decomposition in refluxing xylene, gave rise to the alpha-methoxy methylenequinone derivative (X). This was then condensed with the lithio derivative of sultam (III) to form selectively the desired E-adduct. In an analogous procedure, aldehyde (VIII) was converted to the chloromethylene compound (XI) with methanesulfonyl chloride and triethylamine in refluxing CH2Cl2. Condensation of (XI) with the lithiated sultam (III) furnished the desired E-benzylidene sultam.