Synthesis of fentanyl analogs

Use of 4-(phenylamino)-4-(methoxymethyl)piperidine (I) for synthesizing sufentanil or alfentanil, is claimed. Independent claims are included for: (1) preparing (I) comprising either (a) reacting 1-benzyl-piperidin-4-one with phenyl amine to obtain 1-benzyl-4-phenylamino-piperidine-4-carbonitrile, hydrolyzing 1-benzyl-4-phenylamino-piperidine-4-carbonitrile under an acid to obtain 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid amide, reacting 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid amide in ethylene glycol using hydrochloric acid or sodium hydroxide to obtain 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid, reacting 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid with dimethyl sulfonate in dimethylformamide to obtain 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid methyl ester, reducing 1-benzyl-4-phenylamino-piperidine-4-carboxylic acid methyl ester with lithium aluminum hydride in toluene to obtain (1-benzyl-4-phenylamino-piperidin-4-yl)-methanol, reacting (1-benzyl-4-phenylamino-piperidin-4-yl) -methanol with sodium hydride and methyl iodide to obtain (1-benzyl-4-methoxymethyl-piperidin-4-yl)-phenyl-amine and hydrogenating (1-benzyl-4-methoxymethyl-piperidin-4-yl)-phenyl-amine using palladium/carbon, or (b) reacting sodium 1-benzyl-4-(phenylamino)piperidine-4-carboxylate with red aluminum in toluene to obtain (1-benzyl-4-phenylamino-piperidin-4-yl)-methanol, reacting (1-benzyl-4-phenylamino-piperidin-4-yl)-methanol with dimethyl sulfonate and tert-butoxide in tetrahydrofuran to obtain (1-benzyl-4-methoxymethyl-piperidin-4-yl)-phenyl-amine and hydrogenating (1-benzyl-4-methoxymethyl-piperidin-4-yl)-phenyl-amine using palladium/carbon in ethanol; (2) preparing alfentanil comprising either reacting (1-ethyl-4-(2-(4-methoxymethyl)-4-(phenylamino)piperidin-1-yl)ethyl)-1H-tetrazol-5(4H)-one (IV) with ethyl ketone compounds of formula (Z-C(=O)-CH 2-CH 3) (III), optionally in the presence of a solvent comprising dimethylformamide, dichloromethane, dimethylsulfoxide and/or tetrahydrofuran, or preparing (1) by the process (a) as above per se, reacting (I) with 1-(2-chloro-ethyl)-4-ethyl-1,4-dihydro-tetrazol-5-one under base to obtain 1-[2-(4-methoxymethyl-4-phenylamino-piperidin-1-yl)-ethyl]-4-methyl-1,4-dihydro-tetrazol-5-one and reacting 1-[2-(4-methoxymethyl-4-phenylamino-piperidin-1-yl)-ethyl]-4-methyl-1,4-dihydro-tetrazol-5-one with propionyl chloride using triethyl amine; (3) preparing sufentanil comprising preparing (1) by the