3-Bromopyridine-4-methanol

To a solution of 3-bromo-4-pyridinecarboxaldehyde 3 (3.0 g, 16.2 mmol) in absolute methanol (40 mL) was added NaBHTo a solution of 3 -bromo-4-pyridinecarboxaldehyde 3 (3.0 g, 16.2 mmol) in absolute methanol (40 mL) was added NaBH4 (0.736 g 19.5 mmol) at 0°C. The mixture was stirred at 0°C for 2 hoursunder nitrogen. The solvent was then removed under vacuum. Water and ethyl acetate were added and the organic layer was washed with water, dried over Na2SO4 and evaporated under vacuum to afford the compound 4 (3.02 1 g, 100percent) as a white powder.‘H NN’IR (CDC13, 300 MHz, 298 K, S ppm): 8.61 (s, 1 H), 8.51 (d, 1H, J 4.8 Hz), 7.55 (d, 1H, J 4.8 Hz), 4.76 (s, 2 H), 2.89 (s, 1 H).‘3C NMR(CDC13, 75.5 MHz, 298 K, S ppm): 151.14, 149.45, 148.54, 122.47, 119.90, 63.47. GCIMS(m/z): 188IR (KBr, v, cm1): 3152, 2894, 2829, 1593, 1447, 1401, 1333, 1223, 1170, 1070, 1024, 834, 705, 599Synthesis 2 (3-Bromo methanol A solution of 3-bromo-pyridine-4-carbaldehyde (5 mmol, 0.93 g) in methanol (10 mL) was cooled to 0 °C under nitrogen. This was treated with sodium borohydride (5.5 mmol, 0.200 g) portionwise, and allowed to stir at 0 °C for 1 hour, then slowly allowed to return to room temperature overnight. The reaction was quenched by the addition of saturated ammonium chloride (5 mL), then evaporated under reduced pressure. The reaction mixture was then diluted with ethyl acetate (20 mL) and washed with water (20 mL). The organic layer was then separated and dried with MgSCU, filtered and evaporated to yield the title compound as a white solid. Yield: 0.94 g, 100percent. LCMS, analytical method 1 , T[0281] To a mixture of 3-bromoisonicotinic acid (2.5 g, 12.37 mmol, leq.) and TEA (3.44 mL, 24.75 mmol, 2.0 eq.) in THF (100 mL) was added methyl chloroformate (1.2 mL, 14.85 mmol, 1.2 eq.) at 0 °C. The mixture was stirred at 0 °C for 10 min and filtered. To this filtrate was added a suspension of NaBHStep 1 ;To a mixture of 3-bromoisonicotinic acid (2.5 g, 12.37 mmol, 1 eq.) and TEA (3.44 mL, 24.75 mmol, 2.0 eq.) in THF (100 mL) was added methyl chloroformate (1.2 mL, 14.85 mmol, 1.2 eq.) at 0° C. General procedure: To a solution of the proper bromopyridine-carbaldehyde (VI, 1 eq.) in MeOH, NaBH4 (2 eq.) was added portionwise. The mixture was stirred at room temperature for 3 hours. After this time, water was added and the mixture was concentrated under vacuum. The residue was diluted with water and extracted with DCM. The combined organic phases were dried over anhydrous MgS04, filtered and evaporated under reduced pressure to give the intermediate compound having general formula VII, which was used in the next step without further purification. (0151) (5-Bromopyridin-3-yl)methanol (Vila). The title compound was obtained according to general procedure B, step 1 using 5-bromopyridine-3-carbaldehyde (Via, 0.25 g, 1.34 mmol), NaBH4 (0.10 g, 2.69 mmol). The crude (0.15 g) was used in the next step without further purification. Yield = 60%.A mixture of To a cooled (-78 C.) solution of Step 1 ;To a mixture of 3-bromoisonicotinic acid (2.5 g, 12.37 mmol, 1 eq.) and TEA (3.44 mL, 24.75 mmol, 2.0 eq.) in THF (100 mL) was added methyl chloroformate (1.2 mL, 14.85 mmol, 1.2 eq.) at 0 C. The mixture was stirred at 0 C. for 10 min and filtered. To this filtrate was added a suspension of NaBH4 (0.95 g, 24.75 mmol, 2 eq.) in water (1.0 mL) at 0 C. The mixture was stirred at 0 C. for 1 h, quenched with NH4Cl(aq) solution, 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

Molecular Weight:188.02
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:186.96328
Monoisotopic Mass:186.96328
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes