反应详情

Stir a solution of trans-cyclopropane-1,2-dicarboxylic acid monomethyl ester (Example 3a) (3.0 g, 20.8 mmol) and TOTU (8.5 g, 26 mmol) in DMF (300 mL) at ambient temperature for 20 min at which time add N-methylmorpholine (2.4 mL 22.9 mmol) and trans 4-methylcyclohexylamine 3.06 g, 27.0 mmol). After 3 h, remove the solvent and dissolve the residue in H2O/EtOAc. Extract the aqueous layer 3 more times with EtOAc and combine the extracts. Wash the extract with saturated NaHCO3 solution, brine and dry over MgSO4. Concentrate the solvent to afford the crude product, and purify by column chromatography over silica gel to give 4.76 g (95%) of colorless crystals, m/z=240 (M+H)+.

1. customremove the solvent
2. dissolutiondissolve the residue in H2O/EtOAc
3. extractionExtract the aqueous layer 3 more times with EtOAc
4. washWash the
5. extractionextract with saturated NaHCO3 solution, brine
6. dry with materialdry over MgSO4
7. concentrationConcentrate the solvent
8. customto afford the crude product
9. custompurify by column chromatography over silica gel