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ChemicalBook CAS DataBase List methyl 4-(chloromethyl)pyridine-2-carboxylate
1206973-14-9

methyl 4-(chloromethyl)pyridine-2-carboxylate synthesis

3synthesis methods
317335-15-2 Synthesis
2-Pyridinecarboxylicacid,4-(hydroxymethyl)-,methylester(9CI)

317335-15-2
86 suppliers
$67.82/250mg

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Yield:1206973-14-9 92%

Reaction Conditions:

with methanesulfonyl chloride;triethylamine in dichloromethane; for 24 h;Reflux;

Steps:

4.1.12. Methyl 4-(chloromethyl)picolinate (20)

General procedure: To a stirred solution of methyl 4-(hydroxymethyl)picolinate 16(0.70 g, 4.1 mmol) in dry CH2Cl2 (40 mL) was added Et3N (1.16 mL,8.3 mmol). The mixture was cooled to 0 °C, and mesyl chloride(0.49 mL, 6.3 mmol) was slowly added. The mixture was then heated for 24 h, and quenched at room temperature with a saturated solution of NaHCO3. The aqueous layer was extracted with EtOAc (x3). The organic phase was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (99/1 CH2Cl2/MeOH) to afford 20 as a brown oil in 92% yield (0.72 g). 1H NMR (300 MHz, CDCl3) δ 8.75(d, J 4.9 Hz, 1H), 8.16 (d, J 1.0 Hz, 1H), 7.52 (dd, J 5.0, 1.7 Hz,1H), 4.61 (s, 2H), 4.03 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.9,149.9, 148.0, 147.3, 125.9, 124.1, 52.7, 43.3. MS (ESI): m/z (%): 188(33), 186 (100) [MH]

References:

Oukoloff, Killian;Coquelle, Nicolas;Bartolini, Manuela;Naldi, Marina;Le Guevel, Rémy;Bach, Stéphane;Josselin, Béatrice;Ruchaud, Sandrine;Catto, Marco;Pisani, Leonardo;Denora, Nunzio;Iacobazzi, Rosa Maria;Silman, Israel;Sussman, Joel L.;Buron, Frédéric;Colletier, Jacques-Philippe;Jean, Ludovic;Routier, Sylvain;Renard, Pierre-Yves [European Journal of Medicinal Chemistry,2019,vol. 168,p. 58 - 77]

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