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A solution of ethyl 4-hydroxy-5-methyl-6-oxo- 1 ,6-dihydropyridine-3-carboxylate (5.0 g, 21.4 mmol) in phosphoryl trichloride (100 mL) was refluxed at 125 °C for 12 h. LCMS monitored the reaction was completed. Most of phosphoryl trichloride was evaporated, and the residue was dropwise added to ice-water (100 mL). The resulting mixture was neutralized with aq. sodium carbonate (50 mL) and extracted with ethyl acetate (200 mL). The organic layer was separated, combined, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column (petroleum ether: ethyl acetate =15:1) to get thetitle compound (1.6 g, 32percent) as a yellow oil. MS (ES+) C9H9C12N02 requires: 232, 234, found:233,235[M+H].
A solution of ethyl 4-hydroxy-5-methyl-6-oxo- 1 ,6-dihydropyridine-3-carboxylate (5.0 g, 21.4 mmol) in phosphoryl trichloride (100 mL) was refluxed at 125 C for 12 h. LCMS monitored the reaction was completed. Most of phosphoryl trichloride was evaporated, and the residue was dropwise added to ice-water (100 mL). The resulting mixture was neutralized with aq. sodium carbonate (50 mL) and extracted with ethyl acetate (200 mL). The organic layer was separated, combined, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column (petroleum ether: ethyl acetate =15:1) to get thetitle compound (1.6 g, 32%) as a yellow oil. MS (ES+) C9H9C12N02 requires: 232, 234, found:233,235[M+H].
To a solution of <strong>[252552-10-6]ethyl 4,6-dichloro-5-methylnicotinate</strong> (2.6 g, 11.1 mmol) in acetonitrile (60 mL)was added dropwise 40% methylamine in water (689 mg, 22.2 mmol, 60 mL), and the mixturewas stirred at 50 C for 72 h. LCMS monitored the reaction was completed. The reaction mixture was concentrated and extracted with ethyl acetate (100 mL). The organic layer was separated, combined, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column (petroleum ether: ethyl acetate = 2:1) to get thetitle compound (2.05 g, 81%) as a colorless oil. MS (ES+) C10H13C1N202 requires: 228, 230, found: 229, 231 [M + H].
(4,6-dichloro-5-methylpyridin-3-yl)methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56%
With diisobutylaluminium hydride; In dichloromethane; toluene; at -78.0℃; for 2.0h;
Step 1: (4,6-dichloro-5-methylpyridin-3-yl)methanol To a stirred solution of <strong>[252552-10-6]ethyl 4,6-dichloro-5-methylnicotinate</strong> (1.75 g, 7.48 mmol, Ark Pharm, catNo. AK121795) in methylene chloride (30 mL) at -78 C. was added diisobutylaluminum hydride (1.0 M in toluene, 18.0 mL, 18.0 mmol) dropwise. The resulting mixture was stirred at -78 C. for 2 h then quenched with saturated aqueous NH4Cl. The mixture was warmed to room temperature then extracted with DCM (3*20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with MeOH in DCM (0-5%) to afford the desired product (0.80 g, 56%). LCMS calculated for C7H8Cl2NO (M+H)+: m/z=192.0. Found: 192.0.
With diisobutylaluminium hydride; In dichloromethane; toluene; at -78.0℃; for 1.0h;
To a stirred solution of <strong>[252552-10-6]ethyl 4,6-dichloro-5-methylnicotinate</strong> (6.70 g, 28.6 mmol) in methylene chloride (100 mL), diisobutylaluminum hydride (1.0 M in toluene, 60. mL, 60. mmol) was added dropwise at -78C. After 1 hour, the reaction mixture was quenched with saturated aqueous potassium sodium tartrate (7 mL) then stirred at room temperature overnight. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layers were dried over MgS04, filtered and concentrated under reduced pressure to afford the crude product (5.46 g). LCMS calculated for C7H8CI2NO [M+H]+ m/z: 192.0; Found: 192.0
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