Multi-step reaction with 7 steps
1: 1.) N-methylmorpholine (NMM), isobutyl chloroformate / 1.) THF, -25 deg C, 5 min, 2.) THF, ether, -70 deg C to RT
2: 97 percent / 4 N HCl / dioxane / 1 h / Ambient temperature
3: 1.) hydroxybenzotriazole (HOBt), EDCI, 2.) N-methylmorpholine (NMM) / 1.) DMF, 40 min, 2.) DMF, a) 0 deg C, 2 h, b) RT, overnight
4: 4 N HCl / dioxane / 1 h / Ambient temperature
5: 1.) hydroxybenzotriazole (HOBt), EDCI, 2.) N-methylmorpholine (NMM) / 1.) DMF, 40 min, 2.) DMF, a) 0 deg C, 2 h, b) RT, overnight
6: NaI, NaHCO3 / dimethylformamide / 18 h / Ambient temperature
7: NaBH4 / methanol
With
4-methyl-morpholine; hydrogenchloride; sodium tetrahydroborate; sodium hydrogencarbonate; benzotriazol-1-ol; sodium iodide; isobutyl chloroformate;
In
1,4-dioxane; methanol; N,N-dimethyl-formamide;
DOI:10.1021/jm00099a008