2-Chloro-1-(3,4-difluoro-phenyl)-ethanone synthesis

Yield:51336-95-9 98%

Reaction Conditions:

Stage #1:chloroacetyl chloride with aluminum (III) chloride in dichloromethane for 0.666667 h;Inert atmosphere;Reflux;Friedel-Crafts Acylation;
Stage #2:ortho-difluorobenzene in dichloromethane for 3 h;Reflux;

Steps:

1 Embodiment 1: compound preparation A
By adding methylene chloride to the reaction bottle 450 ml and alchlor 133.5g (1mol), stir. Under the protection of nitrogen, the reaction in the fluid adds by drops the chlorine acetyl chloride 113g (1mol), dropping time of not less than 10 minutes. The end of the dropping, the reaction solution is then heated to reflow the reaction. Reflux reaction 30 minutes later, the reflux lower dropwise 1,2-difluorobenzene 97g (0.85mol), dropping time of not less than 2 hours. After dripping continued to reflux reaction 1 hour. The end of reaction, the reaction cooling to 20 °C, then the reaction solution is poured in slowly 500g ice water, is continuously stirred for 30 minutes. To be after laminating, the water layer is extracted with methylene chloride. Combined with the organic layer by washing with water, saturated sodium bicarbonate wash, wash. Organic layer use excessive amount of magnesium sulfate drying, filtering, concentrating and removing dichloromethane. Get compound A158g, yield 98% ;

References:

Day international Drugs Ltd.;Lu, Xuejiong CN105712889, 2016, A Location in patent:Paragraph 0050; 0051; 0052

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