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Synthesis of cyclopentyl 2-thienyl ketone, tiletamine and tiletamine acid addition salts, such as tiletamine hydrochloride
Synthesis of cyclopentyl 2-thienyl ketone, tiletamine and tiletamine acid addition salts, such as tiletamine hydrochloride
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机译:环戊基2-噻吩基酮,戊巴胺和戊巴胺酸加成盐的合成,例如盐酸戊巴胺
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摘要
A water-scavenging solvent, such a polyphosphoric acid, can be used for the synthesis of cyclopentyl 2-thienyl ketone by the direct acylation of cyclopentanecarboxylic acid without first reacting the cyclopentanecarboxylic acid with thionylchloride to form the acid chloride, while achieving new and unexpected yields. A tiletamine-free base can be made from the cyclopentyl 2-thienyl ketone with a halide in the presence of a solvent for the cyclopentyl 2-thienyl ketone to form a halogenated cyclopentane 2-thienyl ketone, aminating the halogenated cyclopentane 2-thienyl ketone by reaction with an amine, and subjecting the reaction product to thermal rearrangement, in a suitable solvent, and at a sufficient temperature to form tiletamine free base. Each step for the formation of tiletamine free base can be accomplished using the same solvent, e.g., dichlorobenzene so that intermediates need not be isolated between reactions.
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