4-Pyridinemethanol,2-methoxy-(9CI)

Reference To methyl 2-chloroisonicotinate (18, 53.63 g) were added dioxane (150 mL) and sodium methoxide (25.32 g), and the mixture was stirred at reflux temperature for 26 h and then cooled down to room temperature. To the mixture was added acetic acid (28 mL), and the mixture was evaporated in vacuo. To the resulting residue were added ethyl acetate and water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried, filtered, and the filtrate was evaporated in vacuo. The resulting residue was dissolved in THF (300 mL). Under an argon atmosphere, the solution was added dropwise to a suspension of lithium aluminum hydride (11.88 g) in THF (500 mL) at 0 °C over 1 h. Then the reaction mixture was stirred at 0 °C for 2 h. To the mixture was added water (30 mL) dropwise at 0 °C, and then THF (270 mL) was added. The mixture was filtered over celite, and the filtrate was evaporated in vacuo to obtain 19 (33.55 g, 75percent) as a orange oil: To a cold (0° C. ice bath) solution of 2-methoxyisonicotinic acid (0.285 g, 1.861 mmol) in anhydrous tetrahydrofuran (10 mL), under nitrogen, was added N-methylmorpholine (0.215 mL, 1.954 mmol) and then ethyl chloroformate (0.187 mL, 1.954 mmol). After stirring for 20 minutes sodium borohydride (0.211 g, 5.58 mmol) was added portionwise. The mixture was cooled (−78° C. dry ice acetone bath) and methanol (10 mL) was added over 5 minutes. The temperature was then allowed to rise to room temperature and stirring was continued for 16 hours. The reaction was poured onto a pad of silica gel, and eluted with dichloromethane until turbid flow stopped, then 10percent methanol in dichloromethane. The later filtrate was concentrated under reduced pressure, and purified by silica gel column chromatography (24 g SiO2, 0-10percent (20CV) methanol in dichloromethane) to afford the product (0.24 g, 1.725 mmol, 93percent yield) as an amber oil. LCMS (Condition ACN-TFA, ES+) M+H=140.1, broad elution, calculated exact mass=139.06. (2-Methoxy-pyridin-4-yl)-methanol:; (2-Chloro-pyridin-4-yl)-methanol (2.82 g, 19.67 mmol) was refluxed with 25 wt. percent sodium methoxide (25 ml) solution for 24 hr. After cooling to room temperature, the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexane (1:1)) to afford 1.8 g (60percent) of (2-Methoxy-pyridin-4-yl)-methanol as a pale brown oil.

Molecular Weight:139.15
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:139.063328530
Monoisotopic Mass:139.063328530
Topological Polar Surface Area:42.4
Heavy Atom Count:10
Complexity:97.6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes