Ethyl a-chloropropionate

CH3—CO—CHCl—CH3 and CH3—CHCl—CO —OCgHj a chloroethyl methyl ketone and ethyl a chloropropionate... 

Benzotrithiins (349) are accessible by the reaction of benzopentathiepin (347) with alkylidenephosphoranes (Scheme 52) <91TL6345). Intramolecular nucleophilic addition in the dipolar intermediate (348) followed by extrusion of elemental sulfur accounts for the reaction course. Other nucleophiles, such as the anion derived from ethyl a-chloropropionate, also react with (347) in the same way <89H(29)2097). 

Benzopentathiepin (35) reacts with various active methylene compounds such as malononitrile, ethyl cyanoacetate, ethyl acetoacetate, and ethyl a-chloropropionate in the presence of base such as triethylamine or sodium ethoxide to give dithiins, dithioles, or 1,2,4-trithiin in satisfactory yields. In the present reaction benzopentathiepin (35) was found to act as a 1,4-dipole, 1,4-dication, or 1,5-dipole synthons A, B, or C <89H(29)2087>, respectively (Scheme 15). 

The VNS reaction of nitrobenzene with ethyl a-chloropropionate, proceeding in the para-position of the benzene ring, can be followed in situ by the SnAt of fluorine atom in subsequently added l-fluoro-2,4-dinitrobenzene to give 2,4,4 -trinitrodiarylpropionate, which being hydrogenated is transformed into 3-aryloxindole derivative (Scheme 79) [198, 199]. 

A soln. of rac. ethyl a-chloropropionate and -butylamine in hexane treated with yeast lipase Candida cylindracea), and stirred at 2° for 3 h - (S)-N-butyl-a-chloro-propionamide. Y 62% (e.e. 95%). F.e. and with aromatic amines s. V. Gotor et al.. Tetrahedron Letters 29, 6973-4 (1988). 

The resolution of racemic ethyl 2-chloropropionate with aliphatic and aromatic amines using Candida cylindracea lipase (CCL) [28] was one of the first examples that showed the possibilities of this kind of processes for the resolution of racemic esters or the preparation of chiral amides in benign conditions. Normally, in these enzymatic aminolysis reactions the enzyme is selective toward the (S)-isomer of the ester. Recently, the resolution ofthis ester has been carried out through a dynamic kinetic resolution (DKR) via aminolysis catalyzed by encapsulated CCL in the presence of triphenylphosphonium chloride immobilized on Merrifield resin (Scheme 7.13). This process has allowed the preparation of (S)-amides with high isolated yields and good enantiomeric excesses [29]. 

Recently, the VNS intermediates have been used for further introducing electrophiles. For example, reaction of the enolate of ethyl 2-chloropropionate with nitrobenzene followed by subsequent reaction with an alkylating agent gives a series of esters bearing a quaternary center (Eq. 9.36).63... 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

A. Ethyl 3-iodoproplonate. A 1-L, round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser is charged with ethyl 3-chloropropionate (27.3 g, 0.2 mol) (Note 1) and acetone (400 mL). Sodium iodide (300 g, 2 mol) (Note 2) is added to the dear solution and the mixture is refluxed for 16 hr. The resulting pale yellow reaction mixture is cooled to room temperature, the stirring bar and reflux condenser are removed and the acetone is removed on a rotary evaporator at AO C/SSO mbar (412 mm). The residue is taken up in diethyl ether (300 mL) and washed with a saturated aqueous solution of sodium... 

Reaction of 2-aminoquinoline either with ethyl 3-chloropropionate for 1 h at 100°C (63YZ682) or with methyl acrylate in the presence of acetic anhydride for 8 h at 120°C (71KGS482) gave 2,3-dihydro-l//-pyrimido[l,2-a]quinolin-3-one (58). 

Reactions of 3-substituted 2-(lV-phenylaminomethyl)piperazines with a slight excess of ethyl 2-chloroacetate under reflux afforded mixtures of 9-substituted 2-phenylperhydropyrido[l,2-a]pyrazin-3- and -4-ones, which could be separated by column chromatography [72JCS(P2)1374], When 2-[(3-trifluoromethylphenyl)aminomethyl]piperidine was heated with optically active ethyl 2-chloropropionate (87MIP1 91TA231), or lactic acid ethyl ester methanesulphonate (91TA231), the product was a C-9a epimeric mixture of 2-(3-trifluoromethylphenyl)-4-methylperhydropyrido[l,2-fl]-pyrazin-3-ones. The reaction between yV-methyl-2-piperidine-carboxamide and hydroxymaleic anhydride in pyridine resulted in 2,3-dimethyl-3-hydroxyperhydropyrido[l,2-a]pyrazine-l,4-dione (74CB2804). 

Epstein, O. L., Savchenko, A. I., Kulinkovich, O. G. On the mechanism of titanium-catalyzed cyclopropanation of esters with aliphatic organomagnesium compounds. Deuterium distribution in the reaction products of (CD3)2CHMgBr with ethyl 3-chloropropionate in the presence of titanium tetraisopropoxide. Russ. Chem. Bull. 2000, 49, 378-380. 

Ethyl lactate can also be converted to (R)-( + )-ethyl 2-chloropropionate (85) by treating it neat with thionyl chloride and a catalytic amount of DMF. By a series of manipulations, shown in Scheme 13, 85 is converted in 7 steps to (— )-Lofexidine (89) [30], a stereoselective a2-adrenoceptor agonist used in the treatment of hypertension. This synthesis takes advantage of two consecutive inversion reactions (2 85 —> 86) to produce the desired stereochemistry... 

There are several advantages to the procedure described here for the synthesis of a-substituted cyclobutanones. The preparation of 1-bromo-l-ethoxycyclopropane is convenient and can be accomplished in good overall yield in only two steps from commercially available ethyl 3-chloropropionate. Metalation of 1-bromo-l-ethoxycyclopropane is rapid and reproducible on a large scale and (l-ethoxy)cyclopropyllithium adds cleanly to a wide variety of... 

Preparative Methods for the synthesis of the parent and the 2-monoalkyl-substituted compounds, reduction of ethyl 3-chloropropionate with sodium-potassium alloy in the presence of chlorotrimethylsilane in ether. A recent modification using ultrasound irradiation is much more convenient and more widely applicable. Other substituted derivatives are prepared by cyclopropanation of alkyl silyl ketene acetals with the Furukawa reagent (diiodomethane/diethylzinc). ... 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

In an attempt to prepare ethyl 3-indolylacetate (225) by the action of ethyl chloroacetate on indole magnesium iodide, only unidentified oily products were obtained under a variety of different experimental conditions. However, when indole magnesium iodide was treated with ethyl -chloropropionate in other, a product, identified as 3-[)3-(l-indolyl)propionyl]indole (226) by its behavior on alkaline hydrolysis and by the number of active hydrogen atoms it contained, was obtained. ... 

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