Butylamine → (3R,5S)-N-butyl-3,5,6-trihydroxyhexanamide

Participants

Reaction Steps

As per the PCT publication number WO2008/044243, the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-3a prepared by the reaction of (3R,5S)-tert-butyl 3,5,6-trihydroxy hexanoate with n-butylamine at 70-80° C. to provide the (3R,5S)—N-butyl-3,5,6-trihydroxyhexanamide, which on further reaction with 2,2-dimethoxy propane to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetamide followed by oxidation with oxalyl chloride provides the compound of formula-3a. The said process involves column chromatography purification in each stage and the amidation reaction take place without usage of solvent. When the present inventors were working on the same reaction, it was surprisingly found that the n-butyl amine reaction with protected dihydroxy compound i.e., tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate in presence of methanol solvent provides the compound with high purity and yield. However, it was observed that when ethanol is used in place of methanol the said reaction was not proceeded further.

Provenance & Evidence