5-METHOXY-PYRIDINE-3-CARBALDEHYDE

White to yellow to orange to brown solid

The bromo compound T (100 mg, 0.53 mmol) was taken in an oven-dried RB equipped with magnetic stir-bar and dissolved in anhydrous THF (1 mL). Then, Isopropylmagnesiumchloride (31 mL, 2.0 M in THF) was syringed in and the reaction mixture was stirred for 2 hours at room temperature. N, N-dimethylformamide (8.5 mL) in tetrahydrofuran (12 mL) was added and stirring was continued for an additional hour. The solution was quenched with 2 N HCl to pH of 3 then partitioned between ethyl acetate and water. The organic layer was separated and concentrated to give a residue which was purified using flash chromatography to give 3-methoxy-5-formylpyridine (4.30 g, 56percent) as an oil. To a stirred solution of 3-bromo-5-methoxypyridine (1.00 g, 5.32 mmol) in a mixed solvent (THF/hexane=1:1, 20 mL) was added n-BuLi (2.5 M, 2.4 mL) at -78°C under N2. After stirring at -78 °C for 15 min DMF (0.54 mL, 6.92 mmol) was added slowly. The mixture was stirred for another 30 min and warmed to 0 °C. The mixture was quenched with 20 mL of aq. NaHCO3, extracted with EA (50 mL x 2). The combined organics was washed with brine (50 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated. The resulted residue was purified by column chromatography eluted with PE/EA (5:1) to give the title product (360 mg, 49percent) as a light yellow solid.b) (1001) 5-Methoxy-3-pyridinecarboxaldehyde (CAS 113118-83-5, 0.07 g, 0.49 mmol) and titanium(IV)isopropoxide (0.36 mL, 1.24 mmol) were added to a solution of intermediate 3 (0.084 g, 0.41 mmol) in anhydrous THF (1 mL) at rt and the reaction mixture was stirred at rt for 18 h. The mixture was distillated and dried in vacuo. Then, anhydrous THF (1 mL) was added and the reaction was cooled to 0 C and a 1.4M solution of methylmagnesium bromide in THFdoluene (1.47 mL, 2.06) was added dropwise and the reaction mixture was stirred at 0 C for 15 min and at rt for 15 h. NH4Cl sat was added and the mixture was extracted with DCM (10 mL x 3 times). The organics layers were dried over MgS04 and concentrated in vacuo. The crude product was purified by flash column chromatography (silica; MeOH (10:1) in DCM 0/100 to 50/50). The desired fractions were collected and concentrated in vacuo to yield a compound that was diluted in DCM and 4N HC1 in l, 4-dioxane was added. The solvents evaporated in vacuo and the product was triturated with diethyl ether to yield product 43 as a white solid.

Molecular Weight:137.14
XLogP3:0.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:137.047678466
Monoisotopic Mass:137.047678466
Topological Polar Surface Area:39.2
Heavy Atom Count:10
Complexity:116
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes