Cyclopentanecarboxylic acids synthesis

Because some of the compounds with general structure 316 have noteworthy pharmacological activities, a number of alternative methods have been developed for the synthesis of the 2-substituted and 2,3-disubstituted derivatives 316. 2-Substituted derivatives of 316 cis, n = 1, 2, 3, 4 trans, n = 2, 3, 4) were prepared (77GEP2643384 80AUP507798) from 312-315 with ethyl benzimidates. The attempted ring closure of trans-2-amino-l-cyclopentanecarboxylic acid to rra/w-fused derivatives failed. In this reac-... 

The short Sanofi route to irbesartan (3) is outlined in Scheme 9.6. Dihydroimidazolone 27, which is prepared from the reaction of 1-amino-cyclopentanecarboxylic acid ester (25) with ethyl pentanimidate (26) in the presence of acetic acid in refluxing xylene, is alkylated with biphenylbenzyl bromide 18 in the presence of sodium hydride in DMF to give 28. Finally, the synthesis of irbesartan (3) is completed by the tetrazole formation from reaction of the nitrile group of 28 with tributyltin azide in refluxing xylene. [See Bernhart et al. (1993a, b).]... 

The malonic ester synthesis can also be used to prepare cvc/ualkane-carboxylic acids. For example, wlien 1,4-dibromobutane is treated with diethyl malonate in the presence of 2 equivalents of sodium ethoxide base, the second alkylation step occurs intnimolcailarly to yield a cyclic product. Hydrolysis and decarboxylation then give cyclopentanecarboxylic acid. I hree-, four-, five-,... 

A synthesis of partially-fluorinated cyclopentanecarboxylic acids based on the cyclization of hepta-1,6-dienes by perfluoroalkyl radicals generated from iodides has been developed (e.g. see Scheme 2) and 1 1 perfluoroalkyl iodide-olefin adducts of the type RpCHg-CHI-CHj CHXY [Rp = perfluoroalkyl X,Y = COgH, CX)2R, CX)R, or CN (R = alkyl)] have proved to be convenient sources of perfluoroalkylated cyclopropanes (e.g. see Scheme 3). F N.m.r. analysis of the 3,3,3-trifluoro-l-iodopropene and 3,3,4,4,4-pentafluoro-l-iodobutene prepared by u.v.-induced addition of trifluoroiodomethane and pentafluoroiodoethane, respectively, across the multiple bond in acetylene has revealed that the irons adducts predominate (CFg-CH CHI, cwr/roras = 1 6.7 CgFs-CHiCHI, cisUrans = -Si). cis-Addition across acetylene is much more important in the case of heptafluoro-2-iodopropane, the ratio of c/j- /ra s-(CFs)2CF-CH CHI being 1 1.78. ... 

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