Improved methods and intermediates thereof for preparing carbamoyloxy methyl triazole cyclohexyl acid compounds are described. These compounds are useful as LPA antagonists. Formula (I).

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Oxidizing a first aromatic compound in the presence of a metal salt to yield a second aromatic compound includes combining the first aromatic compound, the metal salt, and water to yield an aqueous mixture, and heating the aqueous mixture at a temperature exceeding 200° C. to yield a reaction product that includes the second aromatic compound.

Oxidizing a first aromatic compound in the presence of a metal salt to yield a second aromatic compound includes combining the first aromatic compound, the metal salt, and water to yield an aqueous mixture, and heating the aqueous mixture at a temperature exceeding 200° C. to yield a reaction product that includes the second aromatic compound.

Provided is a process for preparing 4-phenyl-1-butyric acid, comprising: reacting 4-phenyl-1-butanol with sodium chlorite, a nitroxyl radical catalyst and sodium hypochlorite in an organic solvent and a phosphate buffer; and quenching the reaction with sodium sulfite to produce 4-phenyl-1-butyric. Also provided is 4-phenyl-1-butyric acid prepared by such a process.

Provided is a process for preparing 4-phenyl-1-butyric acid, comprising: reacting 4-phenyl-1-butanol with sodium chlorite, a nitroxyl radical catalyst and sodium hypochlorite in an organic solvent and a phosphate buffer; and quenching the reaction with sodium sulfite to produce 4-phenyl-1-butyric. Also provided is 4-phenyl-1-butyric acid prepared by such a process.

Provided is a process for preparing 4-phenyl-1-butyric acid, comprising: reacting 4-phenyl-1-butanol with sodium chlorite, a nitroxyl radical catalyst and sodium hypochlorite in an organic solvent and a phosphate buffer; and quenching the reaction with sodium sulfite to produce 4-phenyl-1-butyric. Also provided is 4-phenyl-1-butyric acid prepared by such a process.

The purpose of the present invention is to provide a method for producing a 3-hydroxy-3-methylbutyrate or salt thereof, the method being capable of efficiently producing a highly pure 3-hydroxy-3-methylbutyrate or salt thereof. The highly pure 3-hydroxy-3-methylbutyrate or salt thereof can be efficiently produced by performing at least one of the following operations (a) to (d) on a solution containing 3-hydroxy-3-methylbutyrate and impurities exposed to environments of pH 6.0 or less. (a) Hypochlorous acid or salt thereof is added to the solution. (b) The solution is maintained at 40 to 200° C. for 30 minutes or more, provided that the solution contains hypochlorous acid or salt thereof. (c) Calcium salt is added to the solution, and the precipitated calcium 2,3-dihydroxy-3-methylbutanoate is separated from the liquid phase in which 3-hydroxy-3-methylbutyrate and/or the salt is dissolved. (d) A base is added to the solution to separate the liquid phase in which the salt of 2,3-dihydroxy-3-methylbutanoic acid formed is dissolved and the liquid phase in which 3-hydroxy-3-methylbutyrate and/or salt thereof is dissolved.

The purpose of the present invention is to provide a method for producing a 3-hydroxy-3-methylbutyrate or salt thereof, the method being capable of efficiently producing a highly pure 3-hydroxy-3-methylbutyrate or salt thereof. The highly pure 3-hydroxy-3-methylbutyrate or salt thereof can be efficiently produced by performing at least one of the following operations (a) to (d) on a solution containing 3-hydroxy-3-methylbutyrate and impurities exposed to environments of pH 6.0 or less. (a) Hypochlorous acid or salt thereof is added to the solution. (b) The solution is maintained at 40 to 200° C. for 30 minutes or more, provided that the solution contains hypochlorous acid or salt thereof. (c) Calcium salt is added to the solution, and the precipitated calcium 2,3-dihydroxy-3-methylbutanoate is separated from the liquid phase in which 3-hydroxy-3-methylbutyrate and/or the salt is dissolved. (d) A base is added to the solution to separate the liquid phase in which the salt of 2,3-dihydroxy-3-methylbutanoic acid formed is dissolved and the liquid phase in which 3-hydroxy-3-methylbutyrate and/or salt thereof is dissolved.

The purpose of the present invention is to provide a method for producing a 3-hydroxy-3-methylbutyrate or salt thereof, the method being capable of efficiently producing a highly pure 3-hydroxy-3-methylbutyrate or salt thereof. The highly pure 3-hydroxy-3-methylbutyrate or salt thereof can be efficiently produced by performing at least one of the following operations (a) to (d) on a solution containing 3-hydroxy-3-methylbutyrate and impurities exposed to environments of pH 6.0 or less. (a) Hypochlorous acid or salt thereof is added to the solution. (b) The solution is maintained at 40 to 200° C. for 30 minutes or more, provided that the solution contains hypochlorous acid or salt thereof. (c) Calcium salt is added to the solution, and the precipitated calcium 2,3-dihydroxy-3-methylbutanoate is separated from the liquid phase in which 3-hydroxy-3-methylbutyrate and/or the salt is dissolved. (d) A base is added to the solution to separate the liquid phase in which the salt of 2,3-dihydroxy-3-methylbutanoic acid formed is dissolved and the liquid phase in which 3-hydroxy-3-methylbutyrate and/or salt thereof is dissolved.

An imaging agent and a method of its use for imaging a necrosis in a tissue of a subject. The imaging method may be positron emission tomography (PET). In at least one embodiment the imaging agent comprises 2-deoxy-2-[.sup.18F]fluoroglucaric acid (.sup.18F-FGA), or a pharmaceutically-acceptable salt thereof. The imaging agent may be disposed in a pharmaceutically-acceptable excipient, carrier, diluent, or vehicle. The imaging agent may be contained within a kit. The disclosure includes in at least one embodiment a method of preparing a radiopharmaceutical such as .sup.18F-FGA for use in imaging.