Piperidine phosgene

A quite simple way to form the oxazolo[3,4- ]pyridine or thiazolo[3,4- ]pyridine ring system is to build the five-membered ring, respectively, starting from a 2-hydroxymethyl-piperidine or 2-thiomethyl-piperidine. The reaction of the latter compounds with aldehydes, acetals, phosgene, carbonates, or synthetic equivalents have been known for years and will therefore not be detailed here. Representative and typical examples are summarized in Table 10. 

Chloropropyl)-2-piperidone and 1 -(2-chloroethyl)-2-pyrrolidone were reacted with phosgene in toluene, and the 2-chloro derivatives (466, n = 0, 1, R2 = H, R3 = (CH2), C1, m = 2, 3, R5 = Cl) were then reacted with Meldrum s acid (421) in the presence of triethylamine to give isopropylidene [l-(3-chloroalkyl)piperidin-2-ylidene]malonate and [l-(2-chloroethyl)pyrrolidin-2-ylidene]malonate (468, n = 0, 1 R2 = H ... 

Dimethyl sulfate Phosgene Piperidine Acetic acid... 

Perhydro-oxazolo[3,4- ]pyridines have long been prepared by condensation between the appropriate piperidyl-2-carbinol and an aldehyde or ketone. For example, the antidepressant spiropiperidine derivative (135) is obtained by the reaction between a-phenyl-2-piperidine methanol and N-benzyl-4-piperidone (81USP4260623). Perhydro-oxazolo[3,4-a]pyridin-3-one (136) is obtained by phosgenation of 2-(hydroxymethyl)piperidinium p-toluene sulfonate followed by cyclization of the resultant chloroformate salt by treatment with triethylamine in dichloromethane. This ring system... 

Reaction of arylhydrazones 216 of piperidin-2-ones with methyl chloro-formate, phosgene, or thiophosgene yielded (80USP4213773) the fused-ring system 217. Reaction of 2,2 -azopyridine (218) with diazoalkanes afforded [66JCS(C)78 73LA2088] the 2-(pyrid-2-yl)-l,2,4-triazolo[4,3-a]-... 

Related methods utilizing the reactions of phosgene with ammonia in Me CHOH [2063], or of phosgene with piperidine [1535] have also been described. 

These products may also be prepared from the reaction of COCi, with the hydrochloride salt of the secondary amine [1451]. In some cases, ureas are formed immediately, for example, in the reactions of piperidine [1652] or 2,2 -bipiperidine [668] with phosgene [1652] ... 

Phosgene reacts with amidobenzyl piperidines (substituted at the 2-, 3-, or 4- aromatic ring positions) at room temperature to give the corresponding amidobenzyl chlorides, and a substituted urea. The reaction is typified by that shown for the 2-isomer [1179a] ... 

---