Ethyl chlorofluoroacetate

ETHYL CHLOROFLUOROACETATE (Acetic acid, chlorofluoro-, ethyl ester) 

Caution Hydrogen fluoride vapors are highly corrosive and poisonous. An efficient hood should he used, and rubber gloves should be worn when dismantling the equipment. 

The product, a nearly white oil, settles out as the lower layer. It is separated, washed until free of acid with three 25-ml. portions of saturated sodium bicarbonate solution (Note 2) then with four 25-ml. portions of water, and dried over 10 g. of Drierite. The weight of crude dried ester is 200-210 g. (68-71%). Fractional distillation gives 190-200 g. (65-68% yield) of pure ethyl chloro-fluoroacetate, b.p. 129-130°, d 1.3925 (Note 3). 

The hydrogen fluoride evolved etches the glass reaction vessel, but the same equipment may be used for 4-6 runs. 

If the crude product is not washed free of acid considerable decomposition occurs during distillation with consequent reduction in yield. 

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Hydrogen bromide converts ethyl chlorofluoroacetate to bromofluoroacetic acid. [55] (equation 39). 

Ethyl chlorofluoroacetate has been prepared by the action of sulfuric acid3 or of silica 4 on 2-chloro-l,l,2-trifluoroethyl ethyl ether. The procedure given here is essentially that of Young and Tarrant.3... 

A 1-L three-necked flask was fitted with a gas-tight stirrer, a separatory funnel, and a T-tube to allow the insertion of a thermometer and the escape of HF formed in the reaction. The flask was charged with 25 (137 g, 0.85 mol). The flask was then cooled with an ice bath to a temperature of 5-10 C, and coned H2S04 (93.5 mL, 1.65 mol) was added dropwise to 25 over 30 min. The mixture was stirred for a further 2 h and was then poured onto a mixture of ice (400 g) and H20 (200 mL). The lower layer was separated and washed with a solution of NaHC03 and H20, dried (MgS04), and distilled. Ethyl chlorofluoroacetate (26) was obtained yield 83 g (70%) (distilling at 127-130 C). 

Reaction of Ethyl Chlorofluoroacetate with Grignard Reagents... 

When ethyl chlorofluoroacetate is treated with phenylmagnesium bromide, compound U is formed. This compound reacts with methylmagne-sium bromide to give compound V. Refluxing of the product in tetra-hydrofuran affords compound W. What are compounds U, V, and W, and how are they formed ... 

Reaction of ethyl chlorofluoroacetate with phenylmagnesium bromide at -50° affords U, a ketone, chlorofluoromethyl phenyl ketone. Treatment... 

Similarly, the reaction of ethyl chlorofluoroacetate with sodium diethyl phosphite in CgHg at room temperature affords diethyl l-(ethoxycarbonyl)-l-fluoromethylphosphonate in 40% yield. ... 

O-Ethylcaprolactim, 31, 73 Ethyl a-B-caproylpropionate, 35, 18 Ethyl chloroacetate, 30, 7 34, 54 Ethyl chlorocarbonate, 35, 91 Ethyl chlorofluoroacetate, 34, 49 Ethyl /3-chloroisocrotonate, 32, 78 Ethyl cyanoacetate, 32, 45 35, 7 Ethyl 2-cyano-3-ethyl-3-methylpen-tanoate, 35, 10... 

Both a-fluorocarboalkoxy phosphon ttsf36,37) and a-fluorocarboalkoxy phosphonium saks(38) can be readily prepared from the commercially available ethyl bromofluoroacetate, or this ester can be readily obtained from the commercially available bromotrifluoroethene by application of the Organic Syntheses(39,) preparation of ethyl chlorofluoroacetate. Subsequent deprotonation of either (1) or (2)... 

It is prepared from ethyl chlorofluoroacetate (see below) by conversion to the amide (0.5mol, b 72-77°/lmm) which is added slowly to, P2O5 (0.25mol), and the nitrile (3.5g) is distilled off at 50-70"/atmospheric and redistilled (30g, 66°/atmospheric). It is slowly hydrolysed by H2O but rapidly by aqueous alkali. [Young ... 

Ethyl 4-chlorobutanoate Ethyl chlorofluoroacetate Ethyl chloroformate... 

Also obtained by reaction of ethyl chlorofluoroacetate with p-anisole magne-sinm bromide in ethyl ether at -78° for 2 h (20%) [6088]. 

In many cases synthesis of the fluorinated 1,3-CCC-bielectrophile precursors is the most difficult part of the syuthetic sequeuce and using classical methods is usually accomplished by the use of highly toxic fluoroacetic add derivatives in Claisen condensation with ethyl formiate [81], ethyl chloroformate [95,96], diethy-loxalate [82, 97], acetyl, benzoyl chlorides [82] or Vilsmeier-type formylation [98, 99] (Scheme 13). The product of Vilsmeier-type formylation is 3-dimethylamino-2-fluoroacrolein 54 which reacts with triethyloxonium tetrafluoroborate and dimeth-ylamine to give the vinamidinium salt 55 [91], which also can be used as 1,3-bielectrophile (see Scheme 19). Also Reformatsky-type synthesis of ethyl a-fluoroacetoacetate 52 starting from ethyl chlorofluoroacetate 56 was described in 20 % yield [82]. 

Carboxylic acid esters by heating with an equimolar mixture of phthaloyl chloride and chlorosulfonic acid at 70-250 C gave good yields of the corresponding acid chlorides. Thus, ethyl chlorofluoroacetate, by heating with the mixture at 180 °C, afforded chlorofluoroacetyl chloride (88% yield), but when the ester was heated with chlorosulfonic acid alone the yield of the acid chloride was reduced to 50%. The procedure provides a valuable synthetic route for the direct conversion of carboxylic acid esters into the corresponding acid chlorides (see Chapter 5, p 167). ... 

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