130092-20-5Relevant articles and documents
Preparation method of antihypertensive medicine key intermediate of trans-4-cyclohexyl-L-proline
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, (2018/11/22)
The invention discloses a preparation method of trans-4-cyclohexyl-L-proline. The method comprises the following steps of (1) under the effect of an acid-binding agent, 4S-hydroxy-N-Boc-L-proline ester 6 and sulfonyl chloride are subjected to condensation to generate sulphonate 5, wherein R is C1-4 alkyl; (2) under the effects of a copper catalyst, lithium salt and organic alkali, the sulphonate 5and cyclohexylmagnesium bromide take nucleophilic substitution to generate a compound 4; (3) the compound 4 is hydrolyzed by lithium hydroxide to obtain (4S)-N-Boc-4-cyclohexyl-L-proline (a compound3); (4) the compound 3 is subjected to Boc removal under the condition of hydrochloric acid or trifluoroacetic acid/methylene dichloride; a target product 2 is prepared. The preparation method has thebeneficial effects that the target product structure and chirality are introduced through sulphonate and Grignard reagent nucleophilic substitution; the defects of the existing noble metal reductionmethod are overcome; the operation of the method is simple; the conditions are mild; the yield is good; the chemical purity and the optical purity are very high; the preparation method is suitable forindustrial production.
A practical synthesis of optically active δ-nitro-α-ketoesters and 4-cyclohexyl-proline catalyzed by chiral squamides
Liu, Ri-Long,Yan, Yun-Yun,Zhang, Ting,Zhang, Xue-Jing,Yan, Ming
, p. 1416 - 1422 (2015/12/09)
Inexpensive and readily available squamides derived from 9-amino-9-deoxyepiquinine or 9-amino-9-deoxyepiquinidine were found to be superior catalysts for the asymmetric conjugate additions of t-butyl nitroacetate to β,γ-unsaturated-α-ketoesters. After the subsequent decarboxylation with silica gel, a variety of δ-nitro-α-ketoesters were obtained in good yields and with excellent enantioselectivities. The products were further transformed into ethyl 4-aryl-prolinate via a cascade nitro reduction and amination. A new synthesis of (2S,4S)-4-cyclohexyl-proline was also developed. A practical synthesis of optically active δ-nitro-α-ketoesters and 4-aryl-proline derivatives is described.
Process for preparing (trans)-4-substituted-dl-proline derivatives
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, (2008/06/13)
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