4-Methyl phenylacetic acid

The Curtius rearrangement of the acyl azide derived from optically pure a-methoxy-a-(trifluoro-methyl)phenylacetic acid (MTPA 48) also proceeds with retention of configuration, giving a-methoxy-a-(trifluoromethyl)benzyl isocyanate (49 equation 26). The isocyanate (49) is useful for the determination of the enantiomeric composition of optically active primary and secondary amines. 

More recently (I )-0-acetylmandelic acid [(/ )-99], (S)-a -methoxy-a -(trifluoro-methyl)phenylacetic acid (MTPA) [(5 )-83] and other chiral acids have been used as CSAs. These acids form diastereomeric salts soluble in benzene- /6 or chloroform-d with a wide range of amines and amino alcohols, permitting a direct measure of their enantiomeric composition. EnantiomCTs of l,l -binaphth-2,2 -diol (100) and 1,1 -binaphth-2,2 -diylphosphoric acid (101) and other derivatives of 100 and 101 have also been successfully used as CSAs in chloroform- / and benzene- /6 for the estimation of enantiomeric excesses of a number of -amino alcohols , and enantiomers of 101 have been used for cyclic secondary and tertiary amines . ... 

To a stirred solution of 0.1 mmol (4R,VS)- and (45,l 5 )-4-(l -f rf-butoxycarbonyl-amino-2 -hydroxyethyl)-6-methyl-2-oxo-l,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester in 1 mL anhydrous CH2CI2 were added 29 mg (R)-Qf-methoxy-a -(trifluoro-methyl)phenylacetic acid (0.12 mmol), 25 mg 1,3-dicyclohexylcarbodiimide (0.12 mmol), and a catalytic amount of 4-A, A-(dimethylamino)pyridine. The mixture was stirred for an additional 12 h at room temperature, then concentrated. The residue was taken into EtOAc, washed with saturated aqueous NaHCOs and brine, dried over Na2S04, and concentrated. The residue was purified by preparative TLC, affording the corresponding Mosher ester in almost quantitative yield. 

A diiral GC column has the potential to separate enantiomers of epoxy pheromoies in the Type II class, but die applications are vay limited because no good column with a universal ability fw the resolution has been commercialized. On the odia hand, the resolution abilities of chiral HPLC columns have been examined in detail (77). The Chiralpak AD column qierated under a nmnal-phase oonditiiMi suffidaitly separates the two enantiomers of 9,10-epoxydienes, 6,7-epoxymonoenes and 9,10-epoxy-monoenes. Another normal-phase column, the Chiralpak AS column, is suitable fiir the resolution of the 3,4-epoxydienes. The Chiralcel OJ-R colunm operated unda a reversed-phase condition sufficiently accomplishes the enantiomeric separation of 6,7-epoxydienes and 6,7-epoxymonoenes 18). The stereochemistry of each enantiomer separated by chird HPLC has been studied after methanolysis of the epoity ring. Examining the H NMR data of esters of the produced methoxyalcohols with (S)- and (Ry)-a-methoxy-a-(trifluoro-methyl)phenylacetic acid Ity a modified Mosher s method (79), die parent epoxides widi shorter Rts have been indicated to be (3.9,47 )-, (69,77 )-, and (97 105)-isomers (77). 

The dibenzyl ketone has a very high b.p. (ca. 200°/21 mm.) and this remains in the flask when the unsymmetrical ketone has been removed by distillation. The dialkyl ketone has a comparatively low b.p. and is therefore easily removed by fractionation under normal pressure acetone is most simply separated by washing with water. In this way methyl benzyl ketone (R = CHj), ethyl benzyl ketone (R = CHgCH,) and n-propyl benzyl ketone (R = CHjCHjCH,) are prepared. By using hydrocinnamic acid in place of phenylacetic acid ... 

This procedure is called chloromethylation and will not only turn 1,3-benzodioxole into a methyl chloride but will work equally well in converting plain old benzene into benzyl chloride. Both are important stepping stones towards the production of X and meth. For example, benzyl chloride is a schedule I controlled substance because it will beget benzaldehyde and phenylacetonitrile (a precursor for phenylacetic acid). 

Carbocations can also be generated during the electrolysis, and they give rise to alcohols and alkenes. The carbocations are presumably formed by an oxidation of the radical at the electrode before it reacts or diffuses into solution. For example, an investigation of the electrolysis of phenylacetic acid in methanol has led to the identification of benzyl methyl ether (30%), toluene (1%), benzaldehyde dimethylacetal (1%), methyl phenylacetate (6%), and benzyl alcohol (5%), in addition to the coupling product bibenzyl (26%). ... 

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. 

Substituted phenylacetic acids form Kolbe dimers when the phenyl substituents are hydrogen or are electron attracting (Table 2, Nos. 20-23) they yield methyl ethers (non-Kolbe products), when the substituents are electron donating (see also chap. 8). Benzoic acid does not decarboxylate to diphenyl. Here the aromatic nucleus is rather oxidized to a radical cation, that undergoes aromatic substitution with the solvent [145]. 

Lithium enolates of carboxylic acids such as phenylacetic acid or of amides such as N-methyl-N-phenylvaleric acid amide 1974 are oxidized by BTSP 1949 to a-hydroxy acids, which are isolated after esterification, e.g., to 1973, or to a-hydroxyamides such as 1975 [155] (Scheme 12.43) (cf. also the formation of 3-hydroxybutyrolactam 1962). 

Synthesis of pyrazole 3 by the Medicinal Chemistry route was straightforward from N-Boc isonipecotic acid (45), so we utilized the route after some optimizations, as summarized in Table 2.4. The key 1,3-diketone intermediate 48 was prepared from 45 without issues. A minor problem in the original route was the exothermic nature of the Claisen condensation between methyl ketone 47 and methyl phenylacetate. Slow addition of l.lequiv of methyl phenylacetate to a mixture of 47, 0.2equiv of MeOH, and 2.5equiv of NaH in THF at room temperature solved this exothermic issue and reduced the amount of self-condensation of... 

Structure-activity studies in the phenylacetic acid antiinflammatory series have shown that inclusion of a methyl group on the benzylic carbon usually leads to maximal activity. It is of note that this... 

Inclusion of basic nitrogen in the p-position is also compatible with antiinflammatory activity in this series. Nitration of phenylacetic acid (27) affords 28. Methyl iodide alkylation of the enolate prepared from 28 using two equivalents of sodium hydride gives 29. This appears to involve an Ivanov intermediate (28a). Catalytic reduction of the... 

Base-catalyzed condensation between phenylacetic acid and phthalic acid produces enol lactone 78, which is reduced to benzoate 79 with HI and phosphorous. Friedel-Crafts cyclization by polyphosphoric acid followed by reduction produces alcohol 80. This alcohol forms ethers exceedingly easily, probably via the carbonium ion. Treatment with N-methyl-4— piperidinol in the presence 6f acid leads to the antidepressant hepzidine (81). 

Dibenzyl ether reacted with Mg after five days of reflux in THF to give phenylacetic acid in 42% yield after carbonation. Maercker(99) was able to obtain a 15% yield of 3-butenoic acid from allyl methyl ether after 56 h of reflux. 

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,... 

Add 0.44 moles ring substituted phenylacetate, 100 g acetic anhydride and 30 g sodium acetate and heat at 145-150° for 18 hours to get ca. 0.4 moles of the methyl-phenylacetate (I). Add (I) and formamide (or N-methyl-formamide for the N-methyl cpd.), heat 4-5 hours at 180-195°, cool and extract with CHC13. Evaporate in vacuum, dissolve residue in 40% sulfuric acid and heat at 90-125° for 5-6 hours. Neutralize and add solid NaOH to precipitate about 50% amphetamine. Treat with 10% sulfuric acid to get the sulfate. 

Periodic acid dihydrate, with iodine and durene to give iododurene, 51, 94 Phenols, from aryl methyl ethers, 53, 93 Phenylacetaldehyde, from 2-lithio-1,3,5-trithiane and benzyl bromide, 51, 43 Phenylacetic acid, bromination, 50, 31... 

FIGURE 3. The NMR spectra of the two racemic diastereomers of lV-(4-methyl-2-pentyl)-a-methoxy-a-trifluoromethylphenylacetamide prepared from racemic a-methoxy-a-(trifluoromethyl)phenylacetic acid [MTPA, ( )-83] and racemic 4-methyl-2-pentylamine [( )-84] (A) 60-MHz proton spectrum in chloroform-4 with tetramethylsilane (TMS) as the internal standard (B) 94.1-MHz fluorine-19 spectrum in chloroform-4 with trifluoroacetic acid as the internal standard. Reprinted with permission from Reference 76. Copyright (1969) American Chemical Society... 

Aryl methyl ketones have been obtained [4, 5] by a modification of the cobalt-catalysed procedure for the synthesis of aryl carboxylic acids (8.3.1). The cobalt tetracarbonyl anion is converted initially by iodomethane into the methyltetra-carbonyl cobalt complex, which reacts with the haloarene (Scheme 8.13). Carboxylic acids are generally obtained as by-products of the reaction and, in several cases, it is the carboxylic acid which predominates. Unlike the carbonylation of haloarenes to produce exclusively the carboxylic acids [6, 7], the reaction does not need photoinitiation. Replacement of the iodomethane with benzyl bromide leads to aryl benzyl ketones in low yield, e.g. 1-bromonaphthalene produces the benzyl ketone (15%), together with the 1-naphthoic acid (5%), phenylacetic acid (15%), 1,2-diphenylethane (15%), dibenzyl ketone (1%), and 56% unchanged starting material [4,5]. a-Bromomethyl ketones dimerize in the presence of cobalt octacarbonyl and... 

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. 

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