Dimethylformamide dimethyl acetal → 1-(Dimethoxymethyl)-4-(1H-imidazol-2-ylmethyl)piperidine

Participants

Reaction Steps

The free base of 4-(1H-imidazol-2-yl-methyl)piperidine (1.0 g, 0.006M) and dimethylformamide dimethylacetal (15 ml) in methanol (20 ml) were heated at 90° C. for 8 hrs. The excess of dimethylformamide dimethylacetal was removed at the reduced pressure to give 4-(1H-imidazol-2-yl-methyl)piperidine carboxaldehyde dimethylacetal. To the mixture of 6-aminopenicillanic acid (1.16 g, 0.0054M) and diisopropyl ethylamine (0.96 ml) in dry chloroform (20 ml) was added the solution (10 ml CHCl3 and 2 ml MeOH) of the above piperidine carboxaldehyde dimethylacetal at 0° C. The reaction was stirred at 0° C. for 1 hr. and then at room temperature for 3 hrs. After this period, the solvent was removed in vacuo and the residue dissolved in water (20 ml). The aqueous solution, washed with ethylacetate was acidified to pH 3 with dilute aqueous HCl and purified on Sephadex LH 20 columns to give [2 S-(2alpha,5alpha,6beta)]-3,3-dimethyl-6-[[[4-(1H-imidazol-2-yl-methyl)-1-piperidinyl]methylene]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid hydrochloride (0.84 g, 33%).

Provenance & Evidence