反应详情

温度

-70 °C

A solution of trans-4-(tert-butoxycarbonylamino-methyl)-cyclohexanecarboxylic acid (obtained according to: EP 0614 911 A1) (34.5 g) and triethylamine (28 ml) in dichloromethane (700 ml) is cooled to −70° C. and treated with methylchloroformate (12.9 ml). The reaction mixture is stirred 0.5 h at −70° C. The temperature is allowed to increase to 0° C. and the solution is stirred another 0.5 h until completion of the reaction. The reaction mixture is taken up in ice-cold dichloromethane, washed with an ice-cold 0.5 N HCl solution, a saturated aqueous sodium carbonate solution and water. The organics are dried over sodium sulfate and concentrated to 41.3 g of mixt-anhydride as an oil. This material is taken up in THF and treated at −70° C. with sodium borohydride (5.90 g), followed by absolute methanol (10 ml). The reaction mixture is stirred 15 h at 0° C. and 1 h at ambient temperature to drive the reaction to completion. A 0.5N HCl solution is then carefully added at 0° C., followed by ethyl acetate. The organics are washed with a saturated aqueous sodium carbonate solution, water, dried over sodium sulfate and concentrated. Chromatography on silica gel (Al) yields trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester as a white powder, melting at 88-89° C. Rf(A1) 0.24.

1. temperatureto increase to 0° C.
2. stirringthe solution is stirred another 0.5 h until completion of the reaction
3. washwashed with an ice-cold 0.5 N HCl solution
4. dry with materialThe organics are dried over sodium sulfate
5. concentrationconcentrated to 41.3 g of mixt-anhydride as an oil
6. additiontreated at −70° C. with sodium borohydride (5.90 g)
7. stirringThe reaction mixture is stirred 15 h at 0° C. and 1 h at ambient temperature
8. customthe reaction to completion
9. washThe organics are washed with a saturated aqueous sodium carbonate solution, water
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated