反应详情

To a solution of 2.92 g (20 mmol) methyl-malonic acid monoethyl ester in 100 ml of tetrahydrofuran 2.86 g (20 mmol) of 3,5-difluorobenzylamine, 3.83 g (20 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, 2.70 g (20 mmol) of 1-hydroxybenzotrizole hydrate and 2.58 g (20 mmol) of N,N-diisopropyl-ethylamine were added. The mixture was stirred at room temperature for 18 h. After concentration in vacuo 0.5 N HCl (50 ml) was added and the mixture was extracted with dichloromethane (three times 50 ml). The combined organic layers were extracted with 0.5 N aqueous NaHCO3 solution, dried (MgSO4) and evaporated on the rotary evaporator. The residue was purified by flash chromatography (hexane/ethyl acetate=3:1) to yield 4.29 g (79%) of the tide compound as white crystalline solid.

1. concentrationAfter concentration in vacuo 0.5 N HCl (50 ml)
2. additionwas added
3. extractionthe mixture was extracted with dichloromethane (three times 50 ml)
4. extractionThe combined organic layers were extracted with 0.5 N aqueous NaHCO3 solution
5. dry with materialdried (MgSO4)
6. customevaporated on the rotary evaporator
7. customThe residue was purified by flash chromatography (hexane/ethyl acetate=3:1)