2-Methoxy-3-pyridinemethanol

Preparation of |(2-Methoxypyridin-3-yl)methanoI To a solution of 2-methoxy-pyridine-3-carbaldehyde (2.03 g, 14.8 mmol) in THF (35 mL) was added sodium tetrahydroborate (617 mg, 16.3 mmol) at rt and the mixture was stirred for 1 h. The mixture was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried over Na S0Sodium borohydride (0.17 g, 4.5 mmol) was dissolved in 20 ml ethanol under argon and the mixture cooled to -40 °C in a cryo-cool. General procedure: [PdCl(ηAlcohol 44 (1.0 g, 7.2 mmol) was dissolved in 35 ml dichloromethane. Thionyl chloride (9.4 ml, 18 mmol) was added drop-wise and with stirring and the mixture was stirred for 1 h at room temperature. The mixture was concentrated under reduced pressure. The residue was re-suspended in dichloromethane and saturated sodium bicarbonate solution was added carefully. The mixture was stirred for 10 min and the organic phase was then separated, dried over magnesium sulphate, filtered and evaporated to give 45 (1.05 g, 6.7 mmol, 93% yield) as a pale yellow oil. Purity 95%. 1H NMR (300 MHz, CDCl3) delta ppm 4.01 (s, 3H, MeO), 4.60 (s, 2H, CH2), 6.90 (dd, J = 5.1, 7.0 Hz, 1H, H-5), 7.65 (d, J = 7.1 Hz, 1H, H-4), 8.13 (d, J = 4.7 Hz, 1H, H-6). UPLC/MS (3 min) retention time 1.46 min. LRMS: m/z no ionization.Step 3: 3-Chloromethyl-2-methoxy-pyridine Thionyl chloride (9.5 mL, 130 mmol) was added portionwise to a solution of To a solution of A solution of To a stirred solution of Triphenyl phosphine (122 mg, 0.467 mmol) in THF (5 ml) was added DIAD (94 mg, 0.467 mmol) at 0C and the reaction mixture was stirred at 0C for 15 minutes. Then N-(2, 3 -Dimethyl -phenyl)-4-hydroxy -benzamide (3) (75 mg, 0.311 mmol) was added to the reaction mixture and stirred for 10 minutes. (2-Methoxy-pyridin-3-yl)- methanol (19) (43 mg, 0.311 mmol) was then added and the reaction mixture was stirred at RT for 16 hours. The reaction mixture was then evaporated to dryness and purified by column chromatography in 100-200 silica using Hexane/EtOAc (5: 1) as eluent to afford compound 65 (25 mg, 22.1%) as white solid.

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