反应详情

温度

50 °C

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+).

1. temperaturecooled to 0° C.
2. stirringstirred at room temperature for 30 min.
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. customevaporated
6. customThus, crude trans-(4-methylaminomethyl-cyclohexyl)-methanol was obtained [MS: 158 (MH+)], which
7. temperaturecooled to −10° C.
8. stirringThen, the reaction mixture was stirred at −10° C. for 30 min. and at room temperature for 1 hour
9. customthe reaction mixture evaporated under reduced pressure
10. additionIt was then poured into 100 ml of an ice/water mixture
11. extractionextracted 3 times with 100 ml of dichloromethane
12. dry with materialThe combined dichloromethane phases were dried over magnesium sulfate
13. customevaporated under reduced pressure
14. customThe residue formed
15. customwas chromatographed on silica gel with a 1:1 v/v mixture of dichloromethane and ethylacetate as the eluent