(3-chloropyrazin-2-yl)methanol

3-Chloropyrazine-2-carboxylic acid (2.97 g, 18.73 mmol, 1 eq.) was dissolved in tetrahydrofuran (75 mL). The solution was stirred in an ice bath and triethylamine (5.2 mL, 37.5 mmol, 2 eq.) was added followed by addition of methyl chloroformate (1.74 mL, 22.5 mmol, 1.2 eq.) dropwise. After 30 m, the reaction was filtered and the solid rinsed with more tetrahydrofuran (10 mL). The tetrahydyofuran solution was stirred in an ice bath and a suspension of sodium borohydride (1.4 g, 37.5 mmol, 2 eq.) in water (3 mL) was added. After 1 h, a saturated aqueous ammonium chloride solution (100 mL) was added to the reaction and the mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic phases were washed with a saturated aqueous sodium chloride solution (25 mL) and dried over sodium sulfate. After filtration and evaporation, the residue was purified by silica gel chromatography (5 - 70percent ethyl acetate/hexanes) to give (3-chloropyrazin-2-yl)methanol (0.84 g, 31percent) as a faintly colored oil.102901 To a solution of 3-chloropyrazine-2-carboxylic acid (2.0 g, 12.70 mmol, 1.0 eq.) andTEA (3.50 mL, 25.40 mmol, 2.0 eq.) in THF (50 mL) was added methyl chloroformate (1.2 mL, 15.20 mmol, 1.2 eq.) atO °C. The mixture was stirred at 0°C for 10 mm and filtered. To thisfiltrate was added a suspension of NaBH4 (0.97 g, 25.40 mmol, 2 eq.) in water (1.0 mL) at 0 °C. The mixture was stirred at 0 °C for 1 h, quenched with NH4C1 (aq) solution, and extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give (3-chloropyrazin-2- yl)methanol (400 mg, 22percent) as a white solid. 1H NMR (400 MHz, MeOD) 8.58 (d, J 2.5 Hz, 1H), 8.38 (d, J= 2.5 Hz, 1H), 4.84 (s, 2H). LRMS (M+HStep 1 Under nitrogen protection, To a solution of 2, 2, 6, 6-tetramethylpiperidine (72.8 g, 516.3 mmol)In 500 mL of dry THF solution, N-BuLi (346 mL, 553.7 mmol, 1.6 mol / L THF) was slowly added dropwise at -78 &After completion of the reaction, the reaction mixture was warmed to 0 ° C and the reaction was continued for 20 min.The reaction mixture was then cooled to -78 ° C, A solution of 2-chloropyrazine (50 g, 436.3 mmol) in THF (100 mL) was added dropwise to the reaction mixture, 30min plus finished, The color of the reaction mixture changed from light yellow to dark brown, The reaction was continued for 10 min at -78-0 degC.DMF (84 ml, 1092 mmol)Was dissolved in THF (50 mL) dropwise dropwise into the reaction mixture, Control the reaction system temperature at -70 ~ -78 , 10min plus finished, The reaction was stirred at -78 ° C for 2 h.To the reaction mixture was then added MeOH (800 mL)To the reaction mixture, NaBH4 (33 g, 868 mmol) was added portionwise, After the addition, the reaction mixture was allowed to rise to room temperature and stirring continued for 2 h, TLC shows the raw material reaction is complete, The reaction solution was quenched with saturated NH4Cl, DCM (1 L x 3) was extracted three times, The organic phase was washed with water, Anhydrous Na2SO4 fully dried, After vacuum evaporation, the residue was purified by silica gel column (PE / EA = 100/1 to 5/1) to give 60 g of the title compound1.44 g of 3-chloro-2-pyrazine methanol, 2 mol% of vanadium nitrate (relative to the substrate 3-chloro-2-pyrazine methanol), Add to the 50mL reaction tube, Add 5mL of acetonitrile, Fill the air ball, close the reaction tube, and raise the temperature to 40 C with stirring.And kept for 10 h, until the reaction is over, and cooled to room temperature.Sampling was analyzed using gas chromatography.The conversion rate of 3-chloro-2-pyrazine methanol is 96.1%.The selectivity of 3-chloro-2-pyrazinecarboxaldehyde is greater than 99%.

Molecular Weight:144.56
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:144.0090405
Monoisotopic Mass:144.0090405
Topological Polar Surface Area:46
Heavy Atom Count:9
Complexity:91
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes