反応 #3055

反応方程式

2,3,4,5-tetrafluorobenzoic acid

thionyl chloride

→

2,3,4,5-tetrafluorobenzoyl chloride

溶媒

N,N-dimethylformamide

反応条件

後処理

1. 1
   その他prepared at 20° C.
2. 2
   温度is heated
3. 3
   温度at reflux for 3 hours
4. 4
   その他the thionyl chloride in excess is evaporated off under vacuum
5. 5
   濃縮the solution is concentrated again at 40° C. under vacuum

実験手順

A suspension of 200 g of 2,3,4,5-tetrafluorobenzoic acid, 225 ml of thionyl chloride and 5 ml of N,N-dimethylformamide, prepared at 20° C., is heated at reflux for 3 hours. After cooling at 40° C., the thionyl chloride in excess is evaporated off under vacuum. The residue is taken up with toluene and the solution is concentrated again at 40° C. under vacuum. Thus 219 g of raw 2,3,4,5-tetrafluorobenzoyl chloride are obtained as a yellowish oil. A mixture of 1200 ml of toluene, 220 g of diethyl malonate and 153 g of magnesium ethylate, prepared at 20° C., is heated one hour at reflux, then it is cooled to 5° C. and the acid chloride above obtained is added thereto, by keeping the temperature below 10° C. After a 30-minutes stirring, the mixture is made acid with concentrated hydrochloric acid and the two phases are separated. The organic phase is diluted with water, made acid with sulfuric acid to pH 1.0 and heated at reflux for 7 hours, namely until the reaction is over. The mixture is cooled, the aqueous phase is separated and the organic one is taken up with water and made basic with sodium hydroxide to a very basic pH value. The aqueous phase is separated and the organic one is again extracted with water. The combined aqueous phases are made acid with concentrated hyarochloric acid to pH 1 and extracted twice with toluene. The toluene phase is concentrated under vacuum, the residue is taken up with 1250 ml of acetonitrile. To this mixture, at first 80 g of sodium bicarbonate and then 110 ml of N-methylpiperazine are added and the reaction mixture is heated 3 hours at reflux. By dilution with water the desired product precipitates and it is then filtered and washed with water. The wet product thus obtained is suspended in toluene and the suspension is evaporated by distillation until the solution becomes anhydrous. This solution contains 0.89 mole of ethyl 2,3,5-trifluoro-4-(4-methylpiperazin-1-yl)benzoylacetate and is directly used for the subsequent step (b).

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