ChemicalBook CAS DataBase List Methyl 6-(hydroxymethyl)nicotinate

Methyl 6-(hydroxymethyl)nicotinate synthesis

5synthesis methods

Product Name:Methyl 6-(hydroxymethyl)nicotinate
CAS Number:56026-36-9
Molecular formula:C8H9NO3
Molecular Weight:167.16

881-86-7

56026-36-9

Step 1. Synthesis of methyl 6-(hydroxymethyl)nicotinate (55): a mixture of methyl 2,5-pyridinedicarboxylate (54; 100.0 g, 0.51 mol), CaCl2 (227.4 g, 2.05 mol), and THF (1100 mL) was mixed with EtOH (1200 mL), and stirred for 30 min. NaBH4 (48.6 g, 1.28 mol) was added in batches at 0 °C. The reaction mixture was stirred at room temperature for 18 hours. Subsequently, saturated NH4Cl solution (1.5 L) and water (2.0 L) were added slowly and extracted with dichloromethane (3 x 3.0 L). The organic phases were combined, dried with MgSO4 and concentrated under reduced pressure to give methyl 6-(hydroxymethyl)nicotinate 55 (82.0 g, 96% yield).

881-86-7
176 suppliers
$28.00/1g

56026-36-9
186 suppliers
$9.00/100mg

Yield:56026-36-9 96%

Reaction Conditions:

Stage #1:dimethyl 2,5-pyridine dicarboxylate with calcium chloride in tetrahydrofuran;ethanol for 0.5 h;
Stage #2: with sodium tetrahydroborate;ethanol in tetrahydrofuran at 0;

Steps:

10.1
Step 1. Synthesis of methyl 6-(hydroxymethyl)nicotinate (55):A mixture of dimethyl pyridine-2,5-dicarboxylate (54; 100.0 g, 0.51 mol), CaCl₂ (227.4 g, 2.05 mol), THF (1100 mL) and EtOH (1200 mL) was stirred for 30 min, NaBH₄ (48.6 g, 1.28 mol) was added portionwise at 0ºC. The mixture was stirred for 18 hours. Saturated NH₄Cl solution (1.5 L) and water (2.0L) was added slowly, and the resulting mixture was extracted with dichloromethane (3 x 3.0 L). The combined organic solvent was dried over MgSO₄ and concentrated to give methyl 6- (hydroxymethyl)nicotinate 55 (82.0 g, 96%).

References:

SIRTRIS PHARMACEUTICALS, INC.;NARAYAN, Radha;DISCH, Jeremy, S.;PERNI, Robert, B.;VU, Chi, B. WO2010/56549, 2010, A1 Location in patent:Page/Page column 103

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