METHYL-(4-METHYL-THIAZOL-2-YLMETHYL)-AMINE DIHYDROCHLORIDE synthesis

Yield:644950-37-8 90%

Reaction Conditions:

Stage #1: methylaminewith titanium(IV) isopropylate in methanol at 0; for 0.25 h;Inert atmosphere;
Stage #2: 4-methyl-thiazole-2-carbaldehyde in methanol;
Stage #3: with methanol;sodium tetrahydroborate at 0 - 20;

Steps:

1.1.6

[0285] Ti(0'PR)₄ (1.3 eq) was added with stirring to MeNH₂ (2.0 M in MeOH, 3 eq) at 0 °C under Ar. After 15 min. 4-methylthiazole-2-carbaldehyde (1 eq) was added, and the solution was stirred for 2-3 h. NaBH₄ (1.4 eq, in batches if large scale) was added and stirred at 0° C to RT overnight, followed by solvent removal in vacuo. The residue was diluted with water/CH₂Cl₂, and a white ppt formed. The mixture was then filtered through Celite to remove the white ppt and the layers were separated. The aqueous layer was extracted with CH₂C1₂ (x3) and the combined organics were dried over Na₂S0₄. The inorganics were filtered off, and the solvent was removed in vacuo to give the crude product. Purification via column chromatography yielded the pure product in 80-90% yield.

References:

WO2011/130383,2011,A1 Location in patent:Page/Page column 83