反应详情

To a stirred solution of 2-Methylsulfanyl-pyrimidine-4-carboxylic acid N-methyl-hydrazide, 15, (15 g, 75.8 mmol) in ethanol (60 mL) is added 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (15.1 g, 75.8 mmol). The reaction mixture is refluxed for 1.5 hour, cooled to room temperature and NaCNBH3 (7.14 g, 113.7 mmol) added. The pH of the reaction mixture is adjusted to 3 with concentrated HCl and the reaction mixture stirred for 3 hours at room temperature. The mixture is neutralized with saturated sodium bicarbonate and extracted three times with CH2Cl2 and the combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (EtOAc) affords 19.7 g (68% yield) of the desired product. 1H NMR (300 MHz, CDCl3) δ 8.70 (q, J=2.9 Hz, 1H), 7.36-7.27 (m, 2H), 2.61 (s, 1H), 4.16 (q, J=6.9 Hz, 1H), 3.97-3.78 (m, 2H), 3.37 (d, J=16 Hz, 3H), 2.91-2.79 (m, 2H), 2.61 (s, 3H), 1.93-1.89 (m, 2H), 1.70-1.65 (m, 2H), 1.48 (d, J=8 Hz), 9H); ESI/MS: 382.3 (M+H).

1. temperatureThe reaction mixture is refluxed for 1.5 hour
2. extractionextracted three times with CH2Cl2
3. dry with materialthe combined organic layers are dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification over silica (EtOAc)