2-methylbutanedioic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml steel autoclave was loaded in a glove box (O2 -content less than 1 ppm) with 2.6 g (20 mmol) of itaconic acid, 150 ml of toluene, 50 ml of methanol, 2.02 g (20 mmol) of triethylamine, 36.0 mg (0.0886 mmol) of [Rh(COD)2 ]BF4, 49 mg (0.0886 mmol) of BPPM and 31.5 mg (0.0886 mmol) of tetrabutylammonium trifluoroacetate. the hydrogenation was carried out at a constant pressure of 6 bar of H2, at 30° C. and with intensive stirring. After a total hydrogenation time of 3 hours the reaction solution was evaporated and the residue was dissolved in 40 ml of 2N sodium hydroxide solution. The aqueous phase was washed with toluene, adjusted to pH 2 with conc. hydrochloric acid, saturated with NaCl and extracted with 3×100 ml of ether. The combined ether phases were dried over Na2SO4 and evaporated. There were obtained 2.4 g (92.3%) of methylsuccinic acid as white crystals. M.p. 111°-112° C. [α]D20 =-16.2° (c=5, EtOH). Optical purity 95.4%. was carried out at a constant pressure of 6 bar of H2, at 30° C. and with intensive stirring After a total hydrogenation time of 3 hours the reaction solution was evaporated the residue was dissolved in 40 ml of 2N sodium hydroxide solution The aqueous phase was washed with toluene extracted with 3×100 ml of ether The combined ether phases were dried over Na2SO4 evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The enantiomer excess (hereinafter referred to as "e.e.") of the resulting methylsuccinic acid was determined as follows. A part (1.32 mg, 0.1 mmole) of the crude product was dissolved in 2 ml of THF and 2 ml of acetonitrile, and 45.4 mg (0.22 mmole) of N,N'-dicyclohexylcarbodiimide, 2.4 mg (0.02 mmole) of 4-dimethylaminopyridine, and 0.01 ml (0.11 mmole) of aniline were added to the solution, followed by stirring at room temperature overnight. The solvent was removed from the reaction mixture by distillation under reduced pressure. The residue was dissolved in chloroform, washed three times with a 5M hydrochloric acid aqueous solution and then once with a saturated sodium hydrogencarbonate aqueous solution in a successive manner, and dried over magnesium sulfate. The solvent was removed, and the crude dianilide was purified by silica gel column chromatography using diethyl ether as an eluent. The purified dianilide was subjected to high performance liquid chromatography (HPLC) using a chromatograph equipped with CHIRALCEL-OD® (manufactured by Daicel Chemical Industries, Ltd.) (eluent: isopropyl alcohol/hexane=10/90 by volume; detection: UV 254 nm; flow rate: 1 ml/min) to determine the e.e. The solvent was removed from the reaction mixture by distillation under reduced pressure The residue was dissolved in chloroform washed three times with a 5M hydrochloric acid aqueous solution once with a saturated sodium hydrogencarbonate aqueous solution in a successive manner, and dried over magnesium sulfate The solvent was removed the crude dianilide was purified by silica gel column chromatography equipped with CHIRALCEL-OD® (manufactured by Daicel Chemical Industries, Ltd.) (eluent: isopropyl alcohol/hexane=10/90 by volume; detection: UV 254 nm; flow rate: 1 ml/min)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 20 ml-volume Schlenk's tube were charged 65.0 mg (0.5 mmole) of itaconic acid and 14.91 mg (0.01 mmole) of [RuH((-)-BINAP)2 ]PF6, and 2.5 ml of tetrahydrofuran (THF) and 2.5 ml (32.7 mmole) of isopropyl alcohol were added thereto. The mixture was heated at reflux in an oil bath at 85° C. for 24 hours. The solvent was removed by distillation under reduced pressure. The residue was dissolved in 20 ml of a 1M sodium hydroxide aqueous solution and washed three times with each 10 ml portions of chloroform. The aqueous layer was adjusted to a pH of 1 with concentrated hydrochloric acid and then extracted three times with each 10 ml portions of diethyl ether. The combined ether layer was dried over magnesium sulfate, and the solvent was removed to give 47 to 60 mg of methylsuccinic acid as a white solid. were added The mixture was heated The solvent was removed by distillation under reduced pressure The residue was dissolved in 20 ml of a 1M sodium hydroxide aqueous solution washed three times with each 10 ml portions of chloroform extracted three times with each 10 ml portions of diethyl ether The combined ether layer was dried over magnesium sulfate the solvent was removed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 10 ml of methanol were added 1.301 g (10 m-mol) of itaconic acid, 1.4 ml (10 m-mol) of triethylamine and 8.8 mg (0.01 m-mol) of rhodium cyclooctadiene BCPM complex perchlorate ([Rh(COD)BCPM]+ClO4-). The mixture was stirred in hydrogen atmosphere at 1 atm. for 20 hours at 20° C. and the reaction mixture was concentrated under reduced pressure. To the residue was added 20 ml of an aqueous solution of 1N-NaOH and the mixture was filtered to remove insoluble matter. The filtrate was made acidic with 6N-HCl and extracted with ether. From the ethereal extract, 2-methylsuccinic acid was obtained quantitatively by distilling off the solvent. It was confirmed that the itaconic acid had been converted by 100% in view of a result of 1H-NMR. [α]D22 =-15.51° (c=2.00, EtOH)(optical yield: 91.9%). the reaction mixture was concentrated under reduced pressure To the residue was added 20 ml of an aqueous solution of 1N-NaOH the mixture was filtered to remove insoluble matter extracted with ether From the ethereal extract

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available dimethyl methylsuccinate (1.57 g, 9.8 mmol) was dissolved in a 3:1 mixed solvent of tetrahydrofuran and water, and lithium hydroxide (4 g, 98 mmol) was added and stirred for 2 days at 40° C. under reflux. After completion of the reaction was confirmed by TLC, the residue was distilled under reduced pressure to afford the title compound. was added under reflux the residue was distilled under reduced pressure