General procedure for the reduction of amides with NaBH4/methanesulphonic acid in DMSO
To a 2-neck 100ml flask are added 16mmol of amide, 1.61g (40mmol9 of NaBH4 and 20ml of DMSO. Methanesulphonic acid (3.4ml, 55mmol) and 20ml DMSO are mixed and added dropwise over a 30 minute period. Gas is evolved and a gelatinous substance is formed, which dissolves when the acid comes to exceed the NaBH4 on a molar basis. If the reduction is to produce a prim. or sec. amine, the reduction is quenched by the addition of 20ml of 10% NaOH. In the case of a tert amine the reaction is kept at 70°C for 2 hrs to liberate the product from the borane complex. Isolation then proceeds in the same way as for prim. and sec. amines. After the quench the product is extracted with 3*10ml DCM, washed with 3*10ml 0.1M NaOH to remove the DMSO, and the product is extracted into 3*10ml 10% HCl. Neutralisation with 10% NaOH is followed by extraction of the product with 3*10ml DCM, drying over CaSO4 and fractional distillation.
hexanamide ---> hexylamine 74%
acetanilide ---> N-ethylanilide 77%
N,N-dimethylbenzamide ---> N,N-dimethylbenzylamine 59%
Both procedures from Vogel, 5th ed., p774