Water → HCID 178484049, compound

Participants

Reaction Conditions

Reaction Steps

2.90 g (11.0 mmol) trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester [U.S. (2000) U.S. Pat. No. 6,022,969 A] dissolved in 15 ml of tetrahydrofuran were added slowly to a suspension of 0.92 g of lithium aluminium hydride in 10 ml of tetrahydrofuran. The reaction mixture was then stirred at 50° C. for 4 hours, cooled to 0° C., treated with 2 g of ice, stirred at room temperature for 30 min., diluted with ethyl acetate, dried over sodium sulfate, filtered and evaporated. Thus, crude trans-(4-methylaminomethyl-cyclohexyl)-methanol was obtained [MS: 158 (MH+)], which was dissolved in 20 ml of methanol, cooled to −10° C. and treated at once with 2.77 g di-tert-butyl-dicarbonate. Then, the reaction mixture was stirred at −10° C. for 30 min. and at room temperature for 1 hour. Subsequently, 5 ml of water and 5 ml of triethylamine were added and the reaction mixture evaporated under reduced pressure. It was then poured into 100 ml of an ice/water mixture and extracted 3 times with 100 ml of dichloromethane. The combined dichloromethane phases were dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was chromatographed on silica gel with a 1:1 v/v mixture of dichloromethane and ethylacetate as the eluent giving 2.5 g (82%) trans-(4-hydroxymethyl-cyclohexylmethyl)-methyl-carbamic acid tert-butyl ester as colorless viscous oil, MS: 257 (M+).

Provenance & Evidence