Methyl a-chloropropionate

The method has been used for the preparation of dihalides, e.g., 1,9-dichlorononane (93%) unsaturated halides, e.g., 11-undecylenyl chloride (83%) halo ethers, e.g., /3-ethoxyethyl chloride (80%) halo ketones, e.g., desyl chloride (79%) halo esters, e.g, methyl a-chloropropionate (71%) halo cyanides, e.g., phenylchloroacetonitrile (80%) and aminoalkyl halides,An interesting isomerisation has been observed in liberating 2-diethylamino-l-chloropropane from its hydrochloride salt l-diethylamino-2-chloropropane is formed. ... 

Cyclopropanes. In the presence of cuprous r-butoxide complexed with tri-/i-butylphosphine, methyl a-chloropropionate and methacrylonitrile react to form the isomeric cyclopropanes (1) and (2) via organo-copper intermediates. No reaction occurs in the absence of the ligand. This reaction was carried out... 

Methyl 4-(chloroformyl)butyrate, 611 Methyl-3-chloropropenoate, 14 Methyl a-chloropropionate, 144 Methyl chlorosulfinate-Dimethyl sulfoxide, 377... 

Finely powdered 95%-Na-methoxide added in small portions at 15-35° with cooling when necessary to a mixture of methyl a-chloropropionate and 2 moles methyl acrylate, stirring continued for ca. 1 hr. dimethyl 1-methyl-1,2-cy do-propanedicarboxylate. Y 70%.—Saponification gives 63% of the cfs-diacid (as the anhydride) and 14% of the frans-diacid. F. e. and methods s. L. L. McGoy, Am. Soc. 80, 6568 (1958). 

It is of interest that reaction of methyl, benzyl, and p-nitrophenyl 2-acetamido-4,6-0-benzylidene-2-deoxy-/3-D-glucopyranosides, and also the corresponding methyl a-D-glucopyranoside derivative, with ( )-2-chloropropionic acid gave, in preponderant yields, the respective 3-0-(D-l-carboxyethyl) derivatives257 only from the last-mentioned reaction was a significant amount of the 3-0-(L-l-carboxy-ethyl) derivative isolated. 

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

Optically active esters of a-chloropropionic acid are precursors of agrochemical compounds. These esters are prepared from lactic acid using the synthesis path described in Figure 1. D-Iactic acid is obtained by fermentation. Initially, this compound was esterified to methyl lactate which itself was transformed to (L) methyl chloropropionate (a-CPM). The content of the minority enantiomer in these three compounds was of between 1.5 and 2.5%. 

It enables direct separation of the methyl and isobutyl esters of a-chloropropionic acid. 

Figure 12 shows an example of analysis of methyl and isobutyl a-chloropropionate samples. 

The pioneering paper on using molecular dynamics simulations to understand chiral gas chromatographic results was done by Konig s group [67]. Experimentally they found the S enantiomer of methyl-2-chloropropionate to be more retained on Lipodex D ([heptakis(3-0-acetyl-2,6-di-0-pentyl)-p-CD] coated on a capillary column) at 333 K. A large separation factor, a = 2.02, corresponding to a AAG = 2 kJ/mol i was observed and an attempt to discern the structural features of the transient complexes was made. 

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

Batchwise operated multipurpose plants are per defmitionem the vehicle for the production of fine chemicals. There are, however, a few examples of fine chemicals produced ia dedicated, coatiauous plants. These can be advantageous if the raw materials or products are gaseous or Hquid rather than soHd, if the reaction is strongly exothermic or endothermic or otherwise hazardous, and if the requirement for the product warrants a continued capacity utilization. Some fine chemicals produced by continuous processes are methyl 4-chloroacetoacetate [32807-28-6] C H CIO [32807-28-6], and malononittile [109-77-3] C2H2N2, made by Lonza dimethyl acetonedicarboxylate [1830-54-2] made by Ube and L-2-chloropropionic acid [107-94-8] C2H C102, produced by Zeneca. 

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). 

Reaction of anthranilonitrile or methyl anthranilate with 3-hydroxy-2-butanone followed by malononitrile gave the pyrrolo [1,2-a] quinazoline 16 (79AP552). Both of the diazine and azole rings of pyrroloquinazolines were also simultaneously formed by cyclization of the anilide 17 derived from 3-chloropropionic acid and 2-aminobenzophenone with potassium cyanide to afford the pyrrolo [1,2-a] quinazoline 18 (68JHC185 71USP3595861). 

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). 

Lappin20,197 reported that the reaction of 2-aminopyridines with alkyl 3-chloropropionates to give the pyrido[l,2-u]pyrimidines (142) is accompanied by the dehydrohalogenation of the propionates. In the case of 2-amino-6-methylpyridine this side reaction becomes exclusive. From alkyl acrylates and 2-aminopyridine or its 4- and 5-methyl derivatives, Lappin obtained a mixture of the pyrido[l,2- ]pyrimidines (142 R = H, 7-Me, 8-Me) and the 2-pyridylaminopropionates (144). In reactions lasting only 2 to 3 hours the pyrido[l,2-u]pyrimidines were mainly formed, whereas in prolonged reactions (20-100 hours) the propionates were the main products. 2-Amino-3-methylpyridine gave only the pyrido[l,2-a]pyrimidine (142 R = 9-Me), whereas from 2-amino-6-methylpyridine only the propionate (144 R = 6-Me) was obtained. 

Staerk, D. U., Shitangkoon, A., and Vigh, G. (1995) Preparative gas chromatographic separation of the enantiomers of methyl-chloropropionate using a cyclodextrin-based stationary phase. J. Chromatogr. A 702, 251-257. 

Figure 1. CD spectra obtained within the n- ir band system of benzophenone upon dissolution in (a) methyl-(S)-2-chloropropionate, (b) (K)-a-phenylglycinol, and (c) (2R,3J )-2,3-butanediol (data adapted from reference [4]).

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). 

Phenylpropionic acid derivatives of general formula 261, functionalised at C-2 with a 3-heterosubstituted benzisothiazole, were patented for use in the treatment and/or prevention of peroxysome proliferator-activated receptor gamma (PPARgamma) mediated diseases [89]. Only the synthesis of the 3-sulfur linked compound 264 (40%) was extensively described starting from methyl 3-[4-(benzyloxy)phenyl]-2-chloropropionate (263) and benzoisothiazol-3(2H)-thione (262) operating in the presence of MeONa/MeOH (Scheme 66). 

Ester synthesis by olefin carbonylation has been known for three decades. For example, Pd(II) chloride in ethanol containing 15% HCl at 80°C and 10 MPa, slowly converts a mixture of CO and ethylene to ethyl propionate. The by-products, obtained in small amounts, are ethyl j8-ethoxypropionate and ethyl y-ketocaproate. Vinyl chloride gives ethyl propionate and ethyl chloropropionate. Terminal olefins of Cj chain length give a mixture of linear and a-methyl acid esters. 

Etherification of 4-hydroxyacetophenone in dimethyl sulphoxide containing potassium carbonate by the slow addition of methyl (S)-2-chloropropionate over 30 mins, and reaction with stirring during 6 hours at ambient temperature (with introduction of more potassium carbonate over a further 5 hours) gave methyl (R)-2-(4-acetylphenoxy)propionate (enantiomeric excess, 86%). 

Drug analogues have previously been derived from saturated cardanol (ref. 2). In more recent work 3-pentadecylphenol and its 6-chloro derivative have been reacted with 2-chloropropionic acid and the derived methyl ester then converted to the hydrazide, reaction of which with cyanogen bromide afforded an aminooxadiazole while acetonylacetone gave a 2,5-dimethylpyrrole derivative (ref. 288). 

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