Phenylacetic acid ester

It was therefore of some interest to so modify the molecule as to maximize this particular activity at the expense of the side effects. In much the same vein as the work on cocaine, the structural requirements for the desired activity had at one time been whittled down to embrace in essence an a-substituted phenylacetic acid ester of ethanolamine (S3). 

The analytical sample of a-methoxy-a-(trifluoromethyl)phenylacetic acid ester is prepared as follows. Into a 5-ml, capped, amber vial equipped with a magnetic stirring bar are placed 20 mg of the reaction product, 1.0 mL of methylene chloride, 87 mg of (+)-a-methoxy-a-(trifluoromethyl)phenylacety1 chloride (Note 22), 4 drops of triethylamine and 1 crystal of 4-dimethyl -am1 nopyridine. The mixture 1s stirred at ambient temperature for 1.5 hr, at which point TLC (Note 26) indicates complete conversion to the ester. 

A sample of E-2-hexen-l-ol in methylene chloride was epoxldized at 20°C with m-chloroperoxybenzoic acid. The resultant racemic epoxy alcohol, upon conversion to the diastereomeric (+)-a-methoxy-a-(trifluoromethyl)phenylacetic acid esters in the manner described above, provided a GC standard for determination of the enantiomeric excess obtained in the asymmetric epoxldatlon. 

The racemic 2,3-diphenylbutane-1,4-diol 8, can be prepared via oxidative coupling of phenylacetic acid esters using TiCVEtaN10 followed by NaBHt/k reduction.11 We have examined the resolution of this valuable racemic diol using B(OH)3 and S-proline. The results are outlined in Scheme 4.llb... 

For the determination of the absolute stereochemistry by NMR spectroscopy, Mosher derivatives are widely used [25]. This method is based on the formation of (R)/(S)-MTPA (a-methoxy-a-(trifluormethyl)phenylacetic acid) esters and comparison of the NMR data of both diastereomers. However, it is limited to compounds with amenable functional groups to be derivatized (typically hydroxy groups) and in some cases the conclusions from the NMR experiments are unsafe. 

Increasing the temperature to 350 °C results in decarbonylation of the phenylpyruvic acid methyl ester derivatives and the phenyl acetic ester is formed with a ratio of 65 % a-ketoester to 35 % acetic acid ester. Until now the industrial process for the synthesis of phenylacetic acid ester has started from benzyl chloride, which is converted to benzyl cyanide by KCN, followed by hydrolysis. Every step of this reaction must be performed in a separate reactor and special measures must be taken for handling large amounts of toxic KCN. The new route is certainly an environmentally benign alternative [8,27]. 

III], (Note 18) as the chiral shift reagent (Note 19). The enantiomeric purity may also be determined by GC analysis (Note 20) of the derived a-methoxy-a-(tr1fluoromethy1)phenylacetic acid esters (Notes 21, 22). An alternative to the distillation method is purification by preparative HPLC (Notes 23, 24), and bulb-to-bulb distillation (Note 25) to give 21.85 g (78%) of (2S,3S)-3-propylox1raneniethanol as a white solid, mp 19 C, [o]q -46.6° (CHCI3, 0 1.0). Analysis by GC of material purified in this manner indicates a chemical purity of >99% (Note 14) and an enantiomeric purity of 96.8% (Notes 20, 21, 22). 

Filtration and rotary evaporation of the filtrate yields (2S,3S)-3-propyloxi-ranemethanol as a pale oil contaminated with nonane (about 8.5 g). The nonane is removed by careful Kugelrohr distillation (25-60°C, 8 mmHg), followed by the product as a colourless oil (b.p. 100-110°C, 8 mmHg). About 3.5 g (75%) [a] o -46.6 (c 1.0, CHCI3) is obtained. A procedure is available for determining the optical purity of the product via its a-methoxy-a-(trifluoromethyl)phenylacetic acid ester (Mosher s ester). ... 

The optical purity is determined to be at least 90% ee by preparation of the bis-a-methoxy-a-(trifluoromethyl)phenylacetic acid ester (Mosher s bis-ester). ... 

J Pestic Sci (J Nippon Noyaku Gakkaishi) 4 143-155 Ohno N, Fujimoto K, Okuno Y, Mizutani T, Hirano M, Yoshioka H (1974) A new class of pyrethroidal insecticides a-substituted phenylacetic acid esters. Agric Biol Chem 38 881-883 Oi N (2005) Development of practical chiral stationary phases for chromatography and their applications. Chromatography 26(l) l-5... 

This product is sufficiently pure for the preparation of phenylacetic acid and its ethyl ester, but it contains some benzyl tso-cyanide and usually develops an appreciable colour on standing. The following procedure removes the iso-cyanide and gives a stable water-white compound. Shake the once-distilled benzyl cyanide vigorously for 5 minutes with an equal volume of warm (60°) 60 per cent, sulphuric acid (prepared by adding 55 ml. of concentrated sulphuric acid to 100 ml. of water). Separate the benzyl cyanide, wash it with an equal volume of sa+urated sodium bicarbonate solution and then with an equal volume of half-saturated sodium chloride solution- Dry with anhydrous magnesium sulphate and distil under reduced pressure. The loss in washing is very small (compare n-Butyl Cyanide, Section 111,113, in which concentrated hydrochloric acid is employed). 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

In this process, penicillin G is first hydrolysed to 6-APA with the acylase derived from Kluyvera citwphila at a slightly alkaline pH (pH 75). Subsequently the 6-APA is incubated with an acylase derived from Pseudomonas mdanogenum and with DL-phenylglydne methyl ester at pH 55. This produces ampiciilin in reasonable yields only because of the specificity of the P. melanogenum enzyme. This enzyme does not react with penicillin G nor phenylacetic acid. 

The stereochemistry of each enantiomer separated by the chiral HPLC has been studied after methanolysis of the epoxy ring. Examining the H NMR data of esters of the produced methoxyalcohols with (S)- and (R)-a-methoxy-a-(tri-fluoromethyl) phenylacetic acid by a modified Mosher s method [181], it has been indicated that the earlier eluting parent epoxides are (3S,4R)-, (6S,7R)-, and (9R,10S)-isomers (Table 7) [75, 76, 179]. The above three chiral HPLC columns show different resolution abilities but a different elution order is not observed. The resolution profile by the reversed-phase OJ-R column has been generalized with molecular shapes of the epoxy compounds considering the... 

Acetic acid, butyl ester Acetic acid, pentyl ester Acetic acid, decyl ester Acetic acid, benzyl ester Acetic acid, benzyl ester Acetic acid, 1-cyclohexenyl ester Acetic acid, 3-cyclohexenyl ester Butyric acid, benzyl ester Phenylacetic acid, propyl ester Oleic acid, methyl ester Linoleic acid, methyl ester Linolenic acid, methyl ester Adipic acid, methyl ester Adipic acid, ethyl ester Adipic acid, diethyl ester Adipic acid, dipropyl ester Adipic acid, (methylethyl)ester Adipic acid,... 

Replacement of the p-aminoacyl moiety with an a-aminoacid derivative such as isoleucyl or cyclohexylglycyl led to a 2- to 4-fold decrease in potency. This was the first indication that SAR between this series and the a-amino acid series was distinct. Early on it was discovered that the "right hand side" amide could be replaced with an ester or acid moiety. This result led to a more systematic exploration of acid substitutions. Ortho-, meta- and para-substituted phenylacetic acid derivatives were prepared, and the latter analog (11, Figure 5) proved to be the first submicromolar inhibitor prepared in this series (IC50 = 510 nM). Grati-fyingly, 11 was devoid of thrombin inhibitory activity [31]. 

The benzyl cyanide, prepared according to the procedure as outlined, is collected over a 50 range. It varies in appearance from a colorless to a straw-colored liquid and often develops appreciable color upon standing. For a product of special purity, it should be redistilled under diminished pressure and collected over a 1-20 range. For most purposes, such as the preparation of phenylacetic acid or ester, the fraction boiling i35-i40°/38 mm. is perfectly satisfactory. 

Ethyl phenylacetate may be prepared by the treatment of benzyl cyanide with alcohol and hydrochloric acid gas.1 It is much more convenient in the laboratory, however, to use sulfuric acid in place of hydrochloric acid in fact, the yields obtained are better than those recorded in the literature. This ester may also be made by the esterification of phenylacetic acid with hydrochloric acid and alcohol 2 or with alcohol and sulfuric acid 3 the following less important methods of preparation may be mentioned the action of benzyl magnesium chloride upon ethyl chlorocarbonate,4 and the action of copper on a mixture of bromobenzene and ethyl chloroacetate at 1800.5... 

Nitrophenylacetic acid has been formed by the nitration of phenylacetic acid 1 by the hydrolysis of its ester 2 or its amid 3 and by the hydrolysis of its nitrile with hydrochloric acid.4... 

Anionicallv Activated Alumina. At this time we had also developed an interest in anionically activated alumina. These basic reagents were active in promoting alkylation(42), condensation(43) and hydrolysis(44) reactions. Thus, we impregnated alumina with sodium hydroxide and used this combination both with and without a phase transfer catalyst (benzyltriethyl ammonium chloride). When BTEAC was added, the conversion to ether was decreased and the formation of ester was noted. In the absence of a phase transfer catalyst, the ether became a minor product and methyl phenylacetate became the major product with coproduction of phenylacetic acid. This ester does not result from esterification of the acid as simple stirring of phenylacetic acid with Na0H/A1203 in methanol does not produce methyl phenylacetate. 

There are at least three possibile ways in which the inhibitor can bind to the active site (1) formation of a sulfide bond to a cysteine residue, with elimination of hydrogen bromide [Eq. (10)], (2) formation of a thiol ester bond with a cysteine residue at the active site [Eq. (11)], and (3) formation of a salt between the carboxyl group of the inhibitor and some basic side chain of the enzyme [Eq. (12)]. To distinguish between these three possibilities, the mass numbers of the enzyme and enzyme-inhibitor complex were measured with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI). The mass number of the native AMDase was observed as 24766, which is in good agreement with the calculated value, 24734. An aqueous solution of a-bromo-phenylacetic acid was added to the enzyme solution, and the mass spectrum of the complex was measured after 10 minutes. The peak is observed at mass number 24967. If the inhibitor and the enzyme bind to form a sulfide with elimination of HBr, the mass number should be 24868, which is smaller by about one... 

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