Preparation method of 3-nitropyridine-2-carbaldehyde_Industrial additives

Background and overview of the preparation method of 3-nitropyridine-2-carbaldehyde

3-Nitropyridine-2-carbaldehyde can be used as a pharmaceutical synthesis intermediate. The intermediate 3-nitro-2 can be prepared by reacting 2-chloro-3-nitropyridine as a raw material with tributylvinyltin. -Vinylpyridine, further prepared by the action of 4-methylmorpholine-N-oxide.

Preparation method of 3-nitropyridine-2-carbaldehyde

Preparation method of 3-nitropyridine-2-carbaldehyde Step 1: 3-nitro-2-vinylpyridine

Dissolve 2-chloro-3-nitropyridine (20g, 126.15mmol) in 1,4 dioxane (378mL), add tributylvinyltin (48g, 151.38mmol), and purge with nitrogen The reaction mixture was degassed for 30 minutes, bis(triphenylphosphine)palladium(II) chloride (4.4 g, 6.3 mmol) was added to the reaction mixture, and stirred at 110°C overnight. The reaction mixture was cooled to room temperature, water was added, and extracted with EtOAc. The organic layer was washed with brine and dried over Na₂SO₄. The organic layer was concentrated in vacuo and purified by silica gel column chromatography with 0-5% dimethyl sulfoxide. Elution with EtOAc in hexane afforded 3-nitro-2-vinylpyridine. ¹HNMR (MHz, DMSO-d6) δ5.741 (dd, J=2.0Hz, J=10.4Hz, 1H), 6.536 (dd, J=2.4Hz, J=16.8Hz, 1H ), 7.134-7.202 (m, 1H), 7.593 (dd, J=4.4Hz, J=8.4Hz, 1H), 8.388 (dd, J=1.6Hz, J=di-tert-butyl dicarbonate 8.4Hz, 1H) , 8.857 (dd, J=0.8Hz, J=4.4Hz, 1H); LC-MS (ESI) m/z151.1[M+H]+.

Preparation method of 3-nitropyridine-2-carbaldehyde Step 2: 3-nitropyridine-2-carbaldehyde

Dissolve 3-nitro-2-vinylpyridine (14g, 93.25mmol) in THF: H₂O (2:1) (560mL), add 4-methyl? Phenoline-N-oxide (16.3 g, 139.87 mmol), tert-butanol (1 mL) and osmium tetroxide (4%, 2 mL). The reaction mixture was stirred at 25 °C for 5 h to form the diol, and sodium metaperiodate (64.87 g, 279.7 mmol) was added to the reaction mixture and stirred at 25 °C for 8 h. The reaction mixture was filtered through celite and washed with EtOAc. The filtrate was extracted with EtOAc. The organic layer was washed with brine and dried over Na₂SO₄ and concentrated to give 3-nitrogen. Pyridine-2-carboxaldehyde. ¹HNMR (MHz, DMSO-d6) δ7.931-7.963 (m, 1H), 8.556 (d, J=8.0Hz, 1H), 9.034-9.046 (m, 1H), 10.147 ( s, 1H); LC-MS (ESI) m/z153.2[M+H]+.

References

[1]WO2011075628