反应详情

温度

0 °C

To a 0° C. solution of 4-{N-[2-(4-fluoro-phenyl)-acetyl]-N′-methyl-N′-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester, 17, (26.7 g, 51.7 mmol) in DMF (50 mL) is slowly added NaH (3.1 g of a 60% dispersion in mineral oil, 77.55 mmol). The reaction mixture is stirred for 0.5 h at 0° C. and then quenched with 1.0 N HCl. The aqueous layer is extracted threee times with CH2Cl2. The combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (100% EtOAc) affords 12 g (45% yield) of the desired product: 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J=4.9 Hz, 1H), 7.35-7.29 (m, 2H), 7.02 (t, J=6.8 Hz, 2H), 6.85 (d, J=5.1 Hz, 1H), 4.42-4.32 (m, 3H), 3.28 (s, 3H), 2.88 (t, 12.8 Hz, 2H), 2.58 (s, 3H), 2.79-2.39 (m, 2H), 1.94 (d, J=11.7 Hz, 2H), 1.50 (s, 9H); ESI/MS: 500.3 (M+H).

1. customTo a 0° C.
2. customquenched with 1.0 N HCl
3. extractionThe aqueous layer is extracted threee times with CH2Cl2
4. dry with materialThe combined organic layers are dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification over silica (100% EtOAc)