Preparation method of nysted reagent

Abstract

The invention relates to a preparation method of a nysted reagent. The preparation method comprises the following steps of: (1) adding zinc powder to a methanol solvent under the protection of nitrogen, dropwise adding alcohol solution of hydrogen chloride under the condition of stirring for reacting at the reflux temperature to activate the zinc powder, cooling to be at the room temperature to separate clear liquid with solid, heating the solid, reducing pressure and evaporating the solid to be dry through a water pump to prepare the activated zinc powder; (2) adding the activated zinc powder and a copper catalyzer to the organic solvent, dropwise adding dibromomethane slowly for reacting at the reflux temperature, cooling to be at the room temperature, dropwise adding the dibromomethane for the second time, and stirring at the room temperature until the zinc powder is reacted completely to obtain milky turbid liquid, namely the nysted reagent. According to the preparation method, the activated zinc powder is synthetized to the nysted reagent on the premise of existence of the catalyzer, the method is simple and practical and is easy to operate, the cost of raw materials is low, the economic benefit is good, the pollution to the environment is low, the yield is improved due to the use of the catalyzer, and the final yield achieves more than 90%. The preparation method is suitable for mass industrial production.

Description

Technical field [0001] The invention belongs to the field of fine chemicals and relates to a preparation method of Nastel reagent. Background technique [0002] Nysted Reagent, CAS (Chemical Substance Registration Number): 41114-59-4, Molecular Formula: C 6 H 12 Br 2 OZn 3 , The pure product is a white powdery solid. It is generally formulated as a white THF suspension with a mass percentage concentration of 20% and a molecular weight of 456. The role of Nastel reagent is to convert ketone compounds into corresponding methylene derivatives, which are mainly used in the synthesis of pharmaceutical intermediates, such as the anti-hepatitis drug entecavir, which is a good intermediate for the synthesis of methylene drugs. [0003] Compared with the current Witting reagent method of synthesizing methylene compounds, Nastel reagent provides a new method of methylene. The use of Witting reagent to synthesize methylene compounds has the following significant disadvantages: 1) As describe...

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Problems solved by technology

Adopt Witting reagent to synthesize methylene compound and there are following several notable shortcomings: 1) described in Advanced Organic Chemistry, Reactions and Synthesis, 157-166, Witting reagent is very unstable under the existence of air, therefore must do now 2) the synthesis period needed for preparing Witting reagent is longer; 3) the general price of the raw materials needed for preparing Witting reagent is all more expensive, such as the strong base reagent of butyllithium class, which is not particularly suitable for industrial grade applications; 4 ) Since the preparation of Witting reagent is prepared under strong basic conditions, such conditions are not suitable for the preparation of basic sensitive groups, thus limiting the application of this type of substrate

At present, the preparation method of Nast reagent is only described in US3865848, but the yield of Nast reagent prepared is low, and a large amount of dichloroethane is needed

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