反应详情

2-Amino-malonic acid dimethyl ester hydrochloride (8.51 g, 46.3 mmol) and sodium acetate (3.8 g, 46.3 mmol) is added to a mixture of 2-methyl-3-oxo-butyronitrile (3.0 g, 30.9 mmol), methanol (60 ml) and water (12 ml) and stirred at RT for 17 h. The mixture is concentrated in vacuo to 20 ml and extracted with EtOAc. The combined organic layers are dried over MgSO4 and concentrated in vacuo. Methanol (100 ml) and sodium methoxide (5.4 mol/l in MeOH, 6 ml, 32.4 mmol) is added and the mixture stirred at 65° C. for 3 hours. Water is added at RT and the mixture extracted with EtOAc. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 2.2 g (42%). HPLC-MS: M+H=169; tR=0.52 min (METHOD—1).

1. concentrationThe mixture is concentrated in vacuo to 20 ml
2. extractionextracted with EtOAc
3. dry with materialThe combined organic layers are dried over MgSO4
4. concentrationconcentrated in vacuo
5. stirringthe mixture stirred at 65° C. for 3 hours
6. extractionthe mixture extracted with EtOAc
7. dry with materialThe combined organic layers are dried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe product is purified by RP HPLC