2-Piperidinecarboxylic acid

Chemicei Name 1-[2-(4-aminophenyl)ethyl]-4-phenyl-4-piperidinecarboxylic acid ethyl ester dihydrochloride... 

CN 4-(8-chloro-5,6-dihydro-l lJ/-benzo[5,6]cyclohepta[l,2-fo]pyridin-l l-ylidene)-l-piperidinecarboxylic acid ethyl ester... 

C H2 C103 76811-97-7) see Fexofenadine hydrochloride 4-(2-chloro-2-oxoethyl)-l-piperidinecarboxylic acid phe-nylmethyl ester... 

C 4H,N 1529-40-4) see Indecainide [3S-[l(cis),3a,4 3]]-l-l4-cyano-4-(4-fluorophenyl)cyclo-hexyl]-3-methyl-4-phenyl-4-piperidinecarboxylic acid phenylmethyl ester (C3iH,5FN202) see Levocabastine... 

C20H23NO4S 80138-94-9) see Levocabastine tranx-3-methyl-l-[(4-methylphenyl)sulfonyll-4-phenyl-4-piperidinecarboxylic acid phenylmethyl ester (C27H29NO4S 104907-69-9) see Levocabastine ( )-JV-methyl-2-[3-(l-methyl-4-piperidinyl)-l//-indol-S-yllethenesulfonamide... 

A method for regioselective introduction of a bis(methoxycarbonyl)-methyl group into the 4-position of the piperidine skeleton was explored, and this method was applied to the preparation of cis- and rra j-2,4-disubstituted piperidines (e.g., 114) starting from 2-piperidinecarboxylic acid <96TL(37)5715>. 

Certain esters have often been employed in attempts to confer organ selectivity to molecules possessing carboxyl functions. Thus, for example, treatment of piperidinecarboxylic acid 76 with N-hydroxysuccinimide and DCC affords the ester 77. In a convergent synthesis, the anion from diphenylacetonitrile (78) is alkylated with dibromoethane to afford the bromide 79. Alkylation of the piperidine derivative 77 with that halide 79 gives the anti-diarrheal agent difenoximide (80). The same sequence starting with the phenoxyethyl ester 81 gives fetoxylate (82). 

Tetrabutylammonium fluoride Ammonium, tetrabutyl-, fluoride (8) 1-Butanaminium, N,N,N-tributyl-p fluoride (9) (429-41-4) l-Carbethoxy-4-piperidone 1-Piperidinecarboxylic acid, 4-oxo-, ethyl ester (8,9) (29976-53-2)... 

Oxidation of cyclic secondary amines such as pyrrolidine (351) and piperidine (353) with iodosobenzene in water leads to lactams 352 and 354, respectively (88TL6913, 88TL6917) (Scheme 90). Similar oxidation of 2-piperidinecarboxylic acid and 2-pyrrolidinecarboxylic acid is accompanied by decarboxylation. Cyclic tertiary amines 355, 357, and 359 (Eq. 48) are likewise oxidized to the corresponding lactams. Other examples include phencyclidine (360) to A-(l-phenylcyclohexyl)piperidone (361), N-(cyanocyclohexyl)piperidine (362) to A-(l-cyanocyclohexyl)piperidone (363) (Scheme 91), and 1,2,3,4-tetrahydroisoquinoline to 1,2,3,4-tetrahy-droisoquinolinone (Eq. 49). 

Argatroban [74863-84-6] ((2R,4R)-4-methyl-T [A/2-)(3 methyl l,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate) is a potent inhibitor of thrombin formation and activity (49). This agent has been studied in vitro and in a few animal models. Its toxicity and activity in humans are unknown. 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylic acid monohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, ododess, crystalline powder that melts at 220—226°C. It is soluble in methanol, sparingly soluble in ethanol and acetone, slightly soluble in water and isopropyl alcohol, freely soluble in chloroform, and practically insoluble in ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropine to discourage abuse. 

Carbethoxy-4-piperidone 1-Piperidinecarboxylic acid, 4-oxo-, ethyl ester (8,9) (29976-53-2)... 

Finally, also N-alkylated a-aminoacids such as proline, azetidinecarboxylic acid or piperidinecarboxylic acid give the U-5C-4CR but, apart from one example [62], diastereoselectivities are very poor [65],... 

A solution of 30 g the above product in 100 ml of ethanol and 100 ml of 1 N sodium hydroxide solution was stirred for 24 hrs at room temperature. At the end of this period, the solution was neutralized with 1 N hydrochloric acid and then concentrated to 70 ml. The solution was adjusted to pH=ll with 1 N sodium hydroxide solution, washed three times with 100 ml of ethyl acetate, acidified with 1 N hydrochloric acid and then extracted three times with 100 ml of chloroform. The combined chloroform solution was dried over anhydrous sodium sulfate and evaporated to give 28.0 g (97%) of l-[NG-nitro-N2-(3-methyl-8-quinolinesulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid as an amorphous solid. IR (KBr) 3,300, 1,720, 1,630 cm-1. 

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