Methyl 6-(hydroxymethyl)picolinate

White or off-white solid

Into a 100-mL round-bottom flask, was placed a solution of 2, 6-dimethyl pyridine-2, 6- dicarboxylate (950 mg, 4.87 mmol, 1.00 equiv) in a solvent mixture of methanol (33.2 mL) and dichloromethane (14.2 mL). NaB (185 mg, 5.02 mmol, 1.00 equiv) was added to the reaction mixture in several batches at 0°C. The resulting solution was stirred overnight at room temperature, and then it was quenched by the addition of 50 mL of NC1 (aq.). The resulting solution was extracted with 2x50 mL of dichloromethane and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 1-2: 1) as eluent to yield 750 mg (92percent) of methyl 6-(hydroxymethyl)pyridine-2-carboxylate as a white solid.Into a 100-mE round-bottom flask, was placed a solution of 2, 6-dimethyl pyridine-2, 6-dicarboxylate (950mg, 4.87 mmol, 1.00 equiv) in a solvent mixture ofmethanol (33.2 mE) and dichloromethane (14.2 mE). NaI3H4 (185 mg, 5.02 mmol, 1.00 equiv) was added to the reaction mixture in several batches at 0° C. The resulting solution was stirred over night at room temperature, and then it was quenched by the addition of SOmE of NH4C1 (aq.). The resulting solution was extracted with 2x50 mE of dichioromethane and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1:1-2:1) as eluent to yield 750mg (92percent) of methyl 6-(hy- droxymethyl)pyridine-2-carboxylate as a white solid.A suspension of dimethyl 2, 6-pyridine-dicarboxylate (50 g, 0.25 mol) in methanol (400 mL) and tetrahydrofuran (150 mL) was heated to dissolve and while the solution was still hot, it was treated in portions with sodium borohydride (9.1 g, 0.24 mol). The mixture was stirred for 1 hour after the addition, cooled to 25° C., quenched with 10percent citric acid (80 mL), stirred for 15 minutes, filtered, and concentrated. A solution of the concentrate in dichloromethane was dried over sodium sulfate, filtered, and concentrated. A solution of the residue in hot ethyl acetate was allowed to stand for 16 hours at 25° C. The resulting precipitate (23 g) was collected by filtration. The mother liquor was concentrated and the resulted solid was purified by flash chromatography on silica gel eluting with 10percent methanol in dichloromethane to give the crude white solid (24 g). The solid w was crystallized in ethyl acetate to give a total yield of the title compound (36 g, 84percent yield).Methyl (6-hydroxymethyl)-pyridine-2-carboxylate was synthesized using an adapted literature protocol.To a stirring solution of dimethyl-2, 6-pyridinedicarboxylate (1.45 g, 7.44 mmol) in MeOH (36 mL) and DCM (7.2 mL) at 0° C. was added sodium borohydride (563 mg, 14.87 mmol). A solution of pyridine-2, 6-dicarboxylic acid dimethyl ester (2.00 g, 10.2 mmol) inmethanol (100 ml) was cooled to 0 °C. Sodium borohydride (0.78 g, 20.5 mmol) wasadded portion-wise over 40 min. The reaction mixture was stirred for 3 h at roomtemperature and then neutralised with an aqueous saturated NH4Cl solution. After extraction with DCM (3 ×500 mL), the combined organic layers were dried with Na2SO4, filtered and the solvent was removed invacuo. The crude product was purified by column chromatography (hexane:EtOAc, 1:1, then 1:2) to givemono- alcohol 25 as a colourless solid (1.17 g, 68percent)Sodium borohydride (390 mg, 10.3 mmol, 1 eq.) was added slowly at 0°C to a stirred solution of dimethyl pyridine-2, 6-dicarboxylate (2.00 g, 10.3 mmol, 1 eq.) in MeOH/CHIn a solution of compound 30 (9.3 g, 47.7 mmol) in methanol (200 ml) at 0° C. under argon, sodium borohydride (6.32 g, 166.3 mmol) was slowly. The reaction mixture was stirred at 0° C. for 3 hrs. Reaction was monitored by TLC. Saturated sodium bicarbonate was added to decompose sodium borohydride. The reaction mixture was concentrated and the solution was extracted with chloroform (3×200 ml). The organic layers were combined and dried over magnesium sulphate. After removing solvent, the white residue was purified on silica gel column (60 g) using 30-40percent ethyl acetate/chloroform as eluent to obtain compound 31 (4.5 g, 56percent). MP=83° C.; RThis compound was synthesized after a published procedure [26]. Dimethyl pyridine-2, 6-dicarboxylate (2.00 g, 10.2 mmol) was dissolved in a 7:3 mixture of dry methanol/chloroform (100 mL), then sodium borohydride (390 mg, 10.3 mmol) was added in small portions at 0 °C. After stirring for 3 h at room temperature, the solution was neutralized with saturated ammonium chloride solution, concentrated to 30 mL in vacuo, and extracted with dichloromethane (3 * 50 mL). The organic layers were combined, dried over sodium sulfate, and the solvent was removed in vacuo. The resulting oil was purified using column chromatography (hexane/ethyl acetate 1:1) to yield 950 mg (55.9percent) of a colorless oil which crystallized upon standing. To a solution of 2-βthyl 6-methyl pyridine-2, 6-dicarboxylate (3.0 g, 14, 3 mmol) in MeOH (20 mL) and CH2CI

Molecular Weight:167.16
XLogP3:0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:167.058243149
Monoisotopic Mass:167.058243149
Topological Polar Surface Area:59.4
Heavy Atom Count:12
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes