Production of 4-carbonyl-(S)-proline derivative

Abstract

Synthesis of antihypertensive Lopli intermediate 4-carbonyl-(S)-proline derivative is carried out by taking 4-carbonyl-L-proline derivative as raw material, and reacting it with oxidant to obtain the final product under action of 2,2,6,6-tetramethyl nitro-oxide free radical piperidine compound. It's simple, has gentle reactive condition and high recovery rate, and can be used for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a synthesis method of a drug intermediate 4-carbonyl-(S)-proline derivative. Background technique [0002] 4-carbonyl-(S)-proline derivatives are an important class of pharmaceutical intermediates, which can be used in the synthesis of some drugs such as spiropril, which are usually oxidized from 4-hydroxy-L-proline derivatives get. [0003] About the oxidation process of described structural intermediate, there are mainly three kinds of existing bibliographical reports: [0004] 1. Swern oxidation [JOC, 1992, 57(19): 5264-8, etc.]; [0005] [0006] The main disadvantage of this method is that low temperature operation is required, the conditions are harsh, and the equipment requirements are high, so it is not suitable for industrial production. [0007] 2. Jones reagent oxidation [J.Am.Chem.Soc., 1957, 79(5): 185-192]; [0008] [0009] or [JOC, 2001, 66(10): 3593-3...

AI Technical Summary

Problems solved by technology

[0014] The catalyst used in this method is expensive and costly, and is not suitable for industrial production

[0015] At present, the main technical problems in the process of oxidizing 4-hydroxy-L-proline derivatives to obtain 4-carbonyl-(S)-proline derivatives are as mentioned above, or the operating conditions are harsh, or the reaction reagents are harmful. environment and human health, or expensive processes, etc.

Not suitable for industrial production

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