Tosylmethyl isocyanide → 1,4-Dioxaspiro[4.5]decane-8-carbonitrile

Participants

Reaction Steps

U.S. Pat. No. 8,314,119 shows synthesis of (4s)-1-azaadamantan-4-ol HCl salt from a 7-step process of: (1) Reducing of 1,4-dioxaspiro[4.5]decan-8-one with TOSMIC giving 1,4-dioxaspiro[4.5]decane-8-carbonitrile; (2) Reducing resulting product with LAH giving 1,4-dioxaspiro[4.5]decan-8-ylmethanamine; (3) Cyclizing resulting product with a double-Mannich type condensation using paraformaldehyde and sulfuric acid to form azaadamantan-4-one; (4) Reducing ketone group of azaadamantan-4-one to an alcohol using NaBH4 in presence of borane-THF complex to form a diastereomeric mixture of 1-azaadamantan-4-ol N-borane complex; (5) Coupling resulting product with 4-chlorobenzoic acid; (6) Separating (4s) isomer by column chromatography (silica gel, using 3:1 hexanes-EtOAc), followed by removing 4-chlorobenzoic acid moiety with NaOH; and (7) Removing BH3 group with HCl giving (4s)-1-azaadamantan-4-ol HCl salt. U.S. Pat. No. 8,314,119 is incorporated herein by reference.

Provenance & Evidence