4-aminocyclohexan-1-ol synthesis

Yield:-

Reaction Conditions:

Stage #1:(+/-)-2-Oxa-3-azabicyclo[2.2.2]oct-5-ene hydrochloride with hydrogen;platinum(IV) oxide under 1500.15 Torr; for 7 h;
Stage #2: with hydrogenchloride in 1,4-dioxane

Steps:

a
To a solution of 30.0 g (0.265 mol) of cyclohexanone oxime in 300 ml of methylene chloride and 38 ml of ethanol was slowly added at 0 ⁰C 34.5 g (0.318 mol) of tert- butyl-hypochlorite. The resulting dark blue solution was cooled to -2O⁰C and then 31.9 g (0.398 mol) of 1 ,3-cyclohexadiene were added and the mixture was stored in a freezer at 5°C for 2 days until the blue color had disappeared. The reaction mixture was concentrated to 50% of its volume and then 600 ml of diethyl ether were slowly added. After stirring overnight the resulting precipitate was isolated by suction to yield 29,0 g of 2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene hydrochloride. 5.0 g (0.045 mol) of this material were hydrogenated with 3.0 g (0.013 mol) platinum oxide at 2 bar hydrogen pressure. After 7 h the catalyst was filtered off and a solution of 20 ml 4 M hydrochloric acid in dioxane was added. After evaporation the residue was recrystallized from 30 ml isopropanol giving 3.1 g of cis-4-aminocyclohexanol hydrochloride.

References:

SANOFI-AVENTIS DEUTSCHLAND GMBH WO2007/12422, 2007, A1 Location in patent:Page/Page column 82-83

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