Methyl -2-chloropropionate

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. 

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) [Pg.536]

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. 

Butyl acrylate has been prepared by direet esterifieaLion/ by debromination of -butyl ,/3-dibromopropionate with zinc, by treatment of either butyl /3-chloropropionate or butyl /3-bromopropionate with diethylaniline, and by the pyrolysis of butyl (3-acetoxypropionated Direct esterification and alcoholysis of methyl or ethyl acrylate have been recommended for the preparation of the higher alkyl acrylates. ... 

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). 

EBrIB ethyl-2-bromoisobutyrate. PEBr l-(bromoethyl) benzene, PECl l-(chloroethyl) benzene, BzBr benzyl bromine, MBrP Methyl-2-bromopro-pionate, MCIP methyl 2-chloropropionate, MClAc methyl chloroacetate... 

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. 

From Ser via methyl 2-benzamido-3-chloropropionate, an azahexadiene was prepared which was photocyclized and hydrolyzed to the bicyclic amino acid 14 which is found in the Atelia Herbert Smithii plant (88JOC4793). 

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. 

Antibiotic was also prepared by syntheses from anhydrous hydroxylamine and methyl-2-acetamido-3-chloropropionate followed by reaction with NaN02 in dilute acetic acid. The prepared racemic product was separated on individual isomers. 

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). 

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. ... 

CH3—CO—CHjj—CHgCl and Cl—CHg—CHg—CO—Q.C Hj /3 chloroethyl methyl ketone and ethyl /3 chloropropionate... 

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