反应详情

To a solution of 2-methyl-4-nitro-pyrazole-3-carbaldehyde (718 mg, 4.63 mmol, intermediate 3) in toluene (100 mL) was added 2-(hydroxymethyl)propane-1,3-diol (700 mg, 6.73 mmol) followed by p-toluenesulfonic acid (88 mg, 0.463 mmol). The reaction mixture was heated at reflux for 18 hr whilst azeotropically removing the water. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with DCM (50 mL) and washed with a saturated aqueous NaHCO3 (50 mL). The organic layer was washed with water (20 mL) and brine (20 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol (trans isomer) as the first eluting isomer as a colourless solid (220 mg, 20%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 6.42 (s, 1H), 4.34 (dd, J=11.6, 4.7 Hz, 2H), 4.12 (s, 3H), 3.81 (t, J=11.5 Hz, 2H), 3.56 (t, J=5.1 Hz, 2H), 2.53-2.38 (m, 1H), 1.67 (t, J=4.6 Hz, 1H).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 18 hr
3. customwhilst azeotropically removing the water
4. concentrationconcentrated under reduced pressure
5. additionThe residue was diluted with DCM (50 mL)
6. washwashed with a saturated aqueous NaHCO3 (50 mL)
7. washThe organic layer was washed with water (20 mL) and brine (20 mL)
8. customseparated
9. dry with materialdried over Na2SO4
10. concentrationconcentrated under reduced pressure
11. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)