Zolpidem-D6 (Not suitable for use with GC/MS) synthesis

Yield:-

Reaction Conditions:

Stage #1: 6-methyl-2-(4-methylphenyl)-imidazo<1,2-a>pyridine-3-acetic acidwith oxalyl dichloride;N,N-dimethyl-formamide in dichloromethane; for 4 h;
Stage #2: dimethylamine-D₆ in dichloromethane; for 1.5 h;

Steps:

37

D6-Zolpidem can be prepared using a modification of the procedure described in US Patent No. 6,281,360. Suspend 5 g of 2-(p-tolyl)-6-methylimidazo[l,2a]pyridine-3-acetic acid zol in 50 ml of dry dichloromethane and add 2.5 g of oxalylchloride. Then, add slowly under stirring 5 drops of dimethylformamide (gas formation occurs) and, after 3 hours, add 1.1 g of oxalylchloride. Stir the reaction mixture for 1 hour then bubble slowly gaseous NH(CU3)2 through the reaction mixture for 1.5 hours. After termination, wash the reaction mixture with 2x10 ml of water, dry the organic phase with sodium sulfate and evaporate the solvent under reduced pressure. After adding 25 ml of ethyl acetate to the rest, a solid precipitates. Filter off the precipitate, wash with 2x5 ml of ethyl acetate and dry in a vacuum oven at 40 degrees C. The yield should be 4.3 g of zO2.

References:

WO2006/91885,2006,A2 Location in patent:Page/Page column 53