反应详情

2-(3-Nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine (6 mmol) was dissolved in CH3CN (20 ml) and formaldehyde (2.4 ml, 37% aqueous) was added. NaBH3CN (607 mg) was added, an exotherm was observed. The pH is monitored every 15 min and adjusted to ˜7 with AcOH. After 45 min, the mixture was concentrated in vacuo and the residue is dissolved in EtOAc, washed with 6N NaOH, 1N NaOH, and 2N HCl (3×). The acid washings were combined, adjusted to ˜pH 10 with solid Na2CO3 and extracted with EtOAc (2×). The EtOAc fractions were combined, dried with Na2SO4, and purified with flash chromatography (SiO2, 95:5:0.5 CH2Cl2:MeOH:NH4OH) to afford 1-methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine.

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionthe residue is dissolved in EtOAc
3. washwashed with 6N NaOH, 1N NaOH, and 2N HCl (3×)
4. extractionextracted with EtOAc (2×)
5. dry with materialdried with Na2SO4
6. custompurified with flash chromatography (SiO2, 95:5:0.5 CH2Cl2:MeOH:NH4OH)