4-Thiazolecarboxaldehyde, 2-(3-pyridinyl)- synthesis

Yield:184679-13-8 71%

Reaction Conditions:

Stage #1: ethyl 2-(pyridin-3-yl) thiazole-4-carboxylatewith diisobutylaluminium hydride in dichloromethane at -78; for 3 h;
Stage #2: with methanol in dichloromethane at -78 - 25;
Stage #3: with water;Rochelle's salt in dichloromethane at 25; pH=7; for 16 h;

Steps:

19.B

A solution containing the product from Example 19A (20 g, 85.5 mmol) in dichloromethane (340 mL) was treated dropwise with DIBAL (86 mL, 1 M in dichloromethane) at -78° C., stirred at -78° C. for 2 hours, treated with DIBAL (43 mL, 1 M in dichloromethane), stirred at -78° C. for 1 hour, treated with methanol (20 mL) at -78° C., warmed to 25° C., treated with dichloromethane (250 mL), saturated aqueous sodium potassium tartrate (350 mL), and pH 7 buffer (300 mL), stirred vigorously with a mechanical stirrer for 16 hours, and filtered through celite. The aqueous phase was washed with chloroform, and the combined organic phase were washed with brine and dried over MgSO₄, filtered and concentrated. The residue was chromatographed on silica gel eluting 0-4% methanol/chloroform to give the title compound (11.61 g, 71% yield).

References:

US2005/131017,2005,A1 Location in patent:Page/Page column 107