Producing Z-isomer of hydrogen bromide salt of 2-aminothiazole derivative

A continuous process for preferentially producing a Z-isomer of a hydrogen bromide salt of a 2-aminothiazole derivative of the formula (IV):

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• wherein R1 and R2 independently represent a lower alkyl group having 1 to 5 carbon atoms, and the wavy line means that this compound is a mixture of the E- and Z-isomers,
• which process comprises:
• continuously feeding thiourea and a 2-alkylidene-4-bromoacetoacetic ester of the formula (V):
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• wherein R1 and R2 have the same meanings as defined above, and the wavy line means that this compound is a mixture of the E- and Z-isomers, into a reaction vessel having at least one agitator,
• reacting the thiourea and the compound of the formula (V) together for a sufficient residence time Rt in the reaction vessel to produce a conversion of the compound of the formula (V) into said compound of the formula (IV), and
• withdrawing a reaction mixture from the reaction vessel containing the compound of the formula (IV) as an effluent.

A process for preferentially producing a Z-isomer of a hydrogen bromide salt of a 2-aminothiazole derivative of the formula (IV):

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• wherein R1 and R2 independently represent a lower alkyl group having 1 to 5 carbon atoms and the wavy line means that this compound is a mixture of the E- and Z-isomers,
• which process comprises:
• reacting thiourea with a 2-alkylidene-4-bromoacetoacetic ester of the formula (V):
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• wherein R1 and R2 have the same meaning as defined above and the wavy line means that this compound is a mixture of the E- and Z-isomers, in a reaction mixture at a reaction temperature of −10 to +45° C. for a reaction time Rt defined by the following inequality:
• 60e(−0.15T)≦Rt≦180e(−0.1T),
• wherein “T” means a reaction temperature of the reaction.