Novel synthesis method for 4,4,4-trifluorobutanol

Abstract

The invention relates to a novel synthesis method for 4,4,4-trifluorobutanol. The method comprises the following steps: (1) enabling diethyl malonate to be subjected to substitution reaction with 2,2,2-trifluoro ethyl p-toluenesulfonate under the catalysis of a basic catalyst, so as to obtain 2-(2,2,2-trifluoro ethyl)-diethyl malonate; (2) enabling 2-(2,2,2-trifluoro ethyl)-diethyl malonate to be subjected to decarboxylic reaction, so as to obtain 4,4,4-trifluoro ethyl butyrate; and (3) reducing 4,4,4-trifluoro ethyl butyrate by a reduction reagent under the catalysis of a catalyst, thereby obtaining 4,4,4-trifluorobutanol. Compared with the prior art, the method disclosed by the invention has the advantages that the raw materials are cheap and readily-available, the cost is low, the number of synthesis steps is small, the operation is convenient and safe, the aftertreatment is simple, the solvent can be cyclically applied mechanically and is environment-friendly, the reaction yield is high, and the product is high in purity and good in quality and is applicable to industrial application.

Description

technical field [0001] The invention relates to the synthesis technology of pharmaceutical intermediates, in particular to a new synthesis method of 4,4,4-trifluorobutanol. Background technique [0002] 4,4,4-Trifluorobutanol, formula C 4 h 7 f 3 O, the relative molecular mass is 128.09, the appearance is a colorless transparent liquid, and its structural formula is as follows: [0003] [0004] Due to the high electronegativity of fluorine atoms, 4,4,4-trifluorobutanol has a strong ability to form hydrogen bonds, and it will generate more stable compounds when interacting with other chemical substances; Fluorine compounds have the characteristics of less dosage, low toxicity, high efficacy, and strong metabolism in the performance of medicines and pesticides. They are widely used as drugs with stronger biological activity and higher selectivity. 4,4,4-Trifluorobutanol can be used in medicine to prepare lactones and lactams (used as central nervous system inhibitors),...

AI Technical Summary

Problems solved by technology

[0008] There are two problems in this route: 1) the raw material of 3-chloro-1,1,1-trifluoropropane is difficult to obtain, and the cost is high; 2) the reduction of 4,4,4-trifluorobutyric acid with lithium tetrahydrogen The processing produces a large amount of aluminum salts, which is difficult to handle, flammable and unsafe when in contact with water solvents

[0011] There are three problems in this route: 1) 1,1,1-trifluoro-2,2,2-trichloroethane, low boiling point, easy to leak, not environmentally friendly

2) The first step of adding 1,1,1-trifluoro-2,2,2-trichloroethane requires a large amount, low yield and high cost

3) The third step is to use palladium carbon to reduce, the cost is relatively high, and it is relatively unsafe during industrial production

[0014] There are three problems in this route: 1) the aftertreatment of phosphorus pentoxide dehydration is troublesome, easily causes solvent burning, unsafe, encounters water and decomposes violently exothermic during quenching reaction, emits poisonous corrosive gas, is not environmentally friendly; 2) the second The first step is to use palladium carbon to catalyze hydrogen reduction, which is complicated, unsafe, and costly; 3) Lithium tetrahydrogen reduces the ester group, and the reaction requirements are strict, and the risk factor for large-scale production operations is high

[0017] This route has been greatly improved compared with other routes, but there are still some problems: 1) the price of 2-bromoethanol is slightly expensive; 2) Grignard reaction is used, the operation requirements are strict, and the risk factor has increased; 3) the yield of this route is low ,higher cost

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