2,3,4,5-Tetrafluorobenzoyl chloride → Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

In a nitrogen atmosphere a 50 gallon kettle was charged with 50.9 kg of tetrahydrofuran, 5.2 kg of monoethyl malonate and about 5 g of 2,2'-dipyridyl. After cooling the mixture to -36° C., 41.6 kg of n-butyllithium (15% in hexane) was added over 3 hours maintaining the temperature at -25° to -35° C. The resultant slurry was cooled further to -60° C. and then treated over about 50 minutes with the acid chloride of part (a) at -62° to -54° C. The green/yellow mixture was stirred for 2 hours at ambient temperature and allowed to warm further overnight. The mixture (-24° C.) was quenched (vacuum) into ambient dilute hydrochloric acid (15 L of muriatic acid and 61 L of deionized water). The quench mixture was separated and the organic phase was washed with 2×40 L of deionized water. The combined aqueous phases were back extracted with 40 L of hexane-ether (1:1). All organic layers were combined and washed with 100 L of saturated sodium bicarbonate solution; again back extracting the aqueous phase with 40 L of hexane-ether (1:1). The combined organic layers were concentrated to an oil in vacuo followed by dissolution in 20 L of hexane and repeated concentration to dryness. The hot oil was finally dissolved in 19 L of hexane. The solution was cooled to -5° C. and the crystallized solids were filtered using 4.8 L of cold (-6° C.) hexane as wash. The material was dried in vacuo at room temperature affording 4234 g of product suitable for use in the next step. A second crop was obtained by concentrating the combined filtrate and wash and cooling to low temperature. The combined yield for the first and second crops was 4841 g (74.9%).

Provenance & Evidence