65148-70-1

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 14, p. 723, 1949 DOI: 10.1021/jo01157a002

InChI:InChI=1/C9H10O3/c1-6-3-2-4-7(5-6)8(10)9(11)12/h2-5,8,10H,1H3,(H,11,12)

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 151-50-8 potassium cyanide 
• 620-23-5 m-tolyl aldehyde 
• 67-66-3 chloroform 
• 56-37-1 N-benzyl-N,N,N-triethylammonium chloride 
• 75-25-2 Bromoform 
• 61560-94-9 3-methylphenyloxoacetic acid 
• 585-74-0 3-Methylacetophenone 
• 28987-79-3 m-tolylmagnesium bromide 
• 53313-96-5 α-hydroxy-3-methylbenzeneacetonitrile 
• 151954-45-9 α-<(trimethylsilyl)oxy>-3-methylphenylacetonitrile 
• 77785-21-8 Methoxymethoxy-m-tolyl-acetic acid ethyl ester 
• 73318-83-9 2-oxo-2-(m-tolyl)acetaldehyde 
• 50891-89-9 5-methyl-benzo[b]thiophene-2,3-dione 

Downstream Products

• 132748-42-6 (S)-2-hydroxy-2-(m-tolyl)acetic acid 
• 51373-14-9 (R)-m-methylmandelic acid 
• 1152170-61-0 methyl 2-hydroxy-2-m-tolylacetate 
• 77062-84-1 methyl 2-hydroxy-2-(3-methylphenyl)acetate 
• 187979-43-7 D-(3-methylphenyl)glycine 
• 530091-78-2 benzyl 2-bromo-2-(m-tolyl)acetate 
• 37051-40-4 ethyl α-bromo-3-methylphenylacetate 
• 61560-94-9 3-methylphenyloxoacetic acid 
• 25297-17-0 2-bromo-2-(m-tolyl)acetic acid 
• 65425-04-9 3-m-tolyl-3H-benzofuran-2-one 

Relevant academic research and scientific papers

The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation

A ruthenocenyl phosphino-oxazoline-ruthenium complex (RuPHOX?Ru) catalyzed asymmetric hydrogenation of α-aryl keto acids has been successfully developed, affording the corresponding chiral α-aryl α-hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed to several chiral building blocks, biologically active compounds and chiral drugs. (Figure presented.).

Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(–)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

The enantioselective resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to >99 % ee) and reaction enantioselectivity (E values up to >200). The dopaminergic agent pemoline, used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy, was synthesized with 98 % ee in a straightforward route by condensing the prepared methyl (R)-(–)-mandelate with guanidine hydrochloride under basic conditions. The desired (R)-(+)-pemoline in optically pure form (>99 % ee) was obtained after two recrystallizations from ethanol. However, it was confirmed by chiral HPLC that optically active pemoline undergoes racemization in methanol solution.

Solid phase behavior in the chiral systems of various 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives

The solid phase behavior of a series of monosubstituted F-, Cl-, Br-, I-, and CH3- and two 2,4-halogen-disubstituted 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives was investigated. The study includes detailed information about melting temperature, melting enthalpy, X-ray diffraction data, as well as selected binary phase diagrams of the respective chiral systems. Aside from the known metastable conglomerate 2-chloromandelic acid, evidence for two more metastable conglomerates was found.

Relationships between the racemic structures of substituted mandelic acids containing 8- and 10-membered hydrogen bonded dimer rings

The structures of 27 monosubstituted mandelic acids, including several of their polymorphs, plus unsubstituted mandelic acid itself (two polymorphs) are investigated for structural similarity. The results, presented pictorially as a structural relationship plot, show that rather more structures are built up from the carboxyl-chain hydroxyl hydrogen bonded dimer than from the conventional carboxylic acid dimer. The results show how all the structures are related and, based on the two types of dimer, the degree of similarity that they possess. Some structures with Z′ > 1 contain both sorts of dimers and there are many examples of isostructural sets within the structures so far determined. We also present an example where analysing similarity in related families of structures highlights a structure that should be present and which has indeed then proceeded to be synthesised and determined.

Lipase-catalyzed enantioselective transesterification toward esters of 2-bromo-tolylacetic acids

Lipases from Candida antarctica, Pseudomonas cepacia and Rhizomucor miehei were tested in the resolution of seven racemic substrates belonging to the (RS)-2-bromo tolyl acetate ester category, but differing either in the position of the methyl substituent on the acyl part of the aromatic ring, or in the structure of the alkyl group. Lipase-catalyzed kinetic resolution via transesterification reaction between the ester and octanol in octane revealed that, of the three enzymes tested, P. cepacia lipase is the most efficient for resolution of the various racemates, with R-enantiopreference. In addition, the position of the methyl substituent was found to play a key role in governing the enantioselectivity of the reaction. Using P. cepacia lipase and 2-bromo-m/p-tolyl- or 2-bromophenylacetic acid esters E-values of 6.

AMINO ACID DERIVATIVES

There is provided amino acid derivatives of formula I, wherein p, q, R 1, R 2, R 3, R 4, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.

Thrombin inhibitors, their preparation and use

PCT No. PCT/SE96/00878 Sec. 371 Date Aug. 7, 1996 Sec. 102(e) Date Aug. 7, 1996 PCT Filed Jul. 2, 1996 PCT Pub. No. WO97/02284 PCT Pub. Date Jan. 23, 1997There is provided amino acid derivative formula I, wherein p, q, R1, R2, R3, R4, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.

β-Cyclodextrin-teba: A new catalyst system for selective synthesis of α-hydroxyacids

The presence of β-cyclodextrin (β-CD) and triethylbenzyl ammonium chloride (TEBA) favors the one-pot reaction of aromatic aldehydes, chloroform and sodium hydroxide to give α- hydroxyarylacetic acids in 81% ~ 89% yields.

Reduction of manganate(VI) by mandelic acid and its significance to development of a general mechanism for oxidation of organic compounds by high-valent transition metal oxides

Results obtained from a study of the oxidation of mandelic acid and cyclobutanol by manganate(VI) indicate that reaction mechanisms traditionally applied to oxidations of this type (i.e., hydrogen atom or hydride ion transfers) may not be correct. Instead it appears that the reaction may be initiated by a 2 + 2 addition of the α-C-H bond to a manganese oxo double bond. This interpretation may be useful in the development of a general mechanism for the oxidation of organic compounds by high-valent transition metal oxides including more common oxidants such as permanganate, ruthenium tetroxide, and chromic acid.