Process for the preparation of substituted octanoyl amides

Process for preparation of compounds of formula I,

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• wherein
• R1 and R2 are, independently of one another, H, C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyloxy, R3 is C1-C6alkyl, R4 is C1-C6alkyl, and R5 is C1-C6alkyl, C1-C6hydroxyalkyl, C1-C6alkoxy-C1-C6-alkyl, C1-C6alkanoyloxy-C1-C6alkyl, C1-C6aminoalkyl, C1-C6alkylamino-C1-C6alkyl, C1-C6-dialkylamino-C1-C6-alkyl, alkanoylamido-C1-C6-alkyl, HO(O)C—C1-C6-alkyl, C1-C6alkyl-O—(O)C—C1-C6alkyl, H2N—C(O)—C1-C6alkyl, C1-C6alkyl-HN—C(C)—C1-C6alkyl or (C1-C6alkyl)2N—C(O)—C1-C6-alkyl,
• a) by reacting a compound of formula II,
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• with an amine of formula R5—NH2 to form a compound of formula III,
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• and
• b) by reducing the azide group of the compound of formula III to the amine group and isolating the compounds of formula I, if necessary with the addition of a salt-forming acid, comprising the preparation of compounds of formula II by
• c1) reacting a compound of formula IV,
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• wherein R6 is C1-C20alkyl, C3-C12cycloalkyl, C3-C12cycloalkyl-C1-C6alkyl, C6-C10aryl or C6-C10-aryl-C1-C6alkyl, with a halogenation agent to form a compound of formula VI, or
• c2) reacting a carboxylic acid of formula V, or a salt of this carboxylic acid,
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• with a halogenation agent to form a compound of formula VI,
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• wherein X is Cl, Br or I,
• d) reacting the compound of formula VI in the presence of an alkali metal or alkaline earth metal hydroxide or an alcohol to form a compound of formula VII,
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• wherein M is an alkali metal, an equivalent alkaline earth metal or the residue of an alcohol minus a hydroxyl group,
• e) hydrolysing the compound of formula VII in the presence of an acid to form a compound of formula VIII,
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• f) substituting the hydrogen atom of the hydroxyl group in the compound of formula VIII and converting it to a leaving group AO to form compounds of formula IX,
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• g) and then reacting the compound of formula IX with an azidation agent to form a compound of formula II, or
• h) reacting the compound of formula VIII directly with a zinc azide/-bis-pyridine complex in the presence of a tertiary phosphine and an azodicarboxylate, if necessary in an organic solvent, to form a compound of formula II.