dimethyl 2-methylbutanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 33 mg (0.031 mmol) of the ferrocenyl bis(phosphonite) prepared in Example 1 and 12 mg (0.031 mmol) of bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium(I) perchlorate in 2 mL of methanol/tetrahydrofuran (1:1) solution is stirred for two hours. Then, to the resultant solution of rhodium complex is added a solution of 490 mg (3.1 mmol) of dimethyl itaconate and 13 mL of methanol in a pressure reactor. The reactor is then pressurized to 1018 psi with hydrogen and the reaction is stirred at ambient temperature for 88 hours. 1H nmr analysis of the reaction mixtures shows a 100% conversion of dimethyl itaconate starting material to product. Workup of the reaction mixture gives 492 mg (99% yield) of desired dimethyl 2-methylsuccinate. the reaction is stirred at ambient temperature for 88 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 16 g, 0.40 mol) in anhydrous toluene (200 mL), a solution of 4-chloro-benzaldehyde (28 g, 0.20 mol) and 2-methyl-succinic acid dimethyl ester (48 g, 0.30 mol) in anhydrous toluene (100 mL) was added dropwise at room temperature under a stream of nitrogen. After being stirred at room temperature for 2 hours, the resulting mixture was diluted by adding 2 N sodium hydroxide (200 mL) dropwise, then heated to 80° C., and stirred at the same temperature for 2 hours. After being cooled to room temperature naturally, the aqueous layer was separated, washed with ethyl acetate (100 mL×3), then acidified with 2 N hydrochloric acid to pH 2, and extracted with ethyl acetate (150 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was precipitated from ethyl acetate/petroleum ether (10:1) to give 2-(4-chloro-benzylidene)-3-methyl-succinic acid (13.4 g, 26%) as a yellow solid. the resulting mixture was diluted heated to 80° C. stirred at the same temperature for 2 hours After being cooled to room temperature naturally the aqueous layer was separated washed with ethyl acetate (100 mL×3) extracted with ethyl acetate (150 mL×3) The combined organic layers were dried over sodium sulfate concentrated in vacuo The residue was precipitated from ethyl acetate/petroleum ether (10:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 20 g, 0.5 mol) in anhydrous toluene (200 mL), a solution of 4-fluoro-benzaldehyde (31 g, 0.25 mol) and 2-methyl-succinic acid dimethyl ester (60 g, 0.38 mol) in anhydrous toluene (100 mL) was added at room temperature under a stream of nitrogen. The resulting mixture was stirred at room temperature for 30 minutes and then quenched by the slow addition of water (20 mL). The mixture was acidified by the addition of concentrated hydrochloric acid, and extracted with ethyl acetate (200 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester (20 g, 33%) as a white solid. 1H NMR (400 MHz, acetone-d6) δ ppm 7.77 (s, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 3.82 (q, 7.2 Hz, 1H), 1.40 (d, J=6.8 Hz, 3H). quenched by the slow addition of water (20 mL) The mixture was acidified by the addition of concentrated hydrochloric acid extracted with ethyl acetate (200 mL×3) The combined organic layers were dried over sodium sulfate concentrated in vacuo The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 33 mg (0.031 mmol) of the ferrocenyl bis(phosphonite) prepared in Example 1 and 12 mg (0.031 mmol) of bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium(I) perchlorate in 2 mL of methanol/tetrahydrofuran (1:1) solution is stirred for two hours. Then, to the resultant solution of rhodium complex is added a solution of 490 mg (3.1 mmol) of dimethyl itaconate and 13 mL of methanol in a pressure reactor. The reactor is then pressurized to 1018 psi with hydrogen and the reaction is stirred at ambient temperature for 88 hours. 1H nmr analysis of the reaction mixtures shows a 100% conversion of dimethyl itaconate starting material to product. Workup of the reaction mixture gives 492 mg (99% yield) of desired dimethyl 2-methylsuccinate. the reaction is stirred at ambient temperature for 88 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 33 mg (0.031 mmol) of the ferrocenyl bis(phosphonite) prepared in Example 1 and 12 mg (0.031 mmol) of bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium(I) perchlorate in 2 mL of methanol/tetrahydrofuran (1:1) solution is stirred for two hours. Then, to the resultant solution of rhodium complex is added a solution of 490 mg (3.1 mmol) of dimethyl itaconate and 13 mL of methanol in a pressure reactor. The reactor is then pressurized to 1018 psi with hydrogen and the reaction is stirred at ambient temperature for 88 hours. 1H nmr analysis of the reaction mixtures shows a 100% conversion of dimethyl itaconate starting material to product. Workup of the reaction mixture gives 492 mg (99% yield) of desired dimethyl 2-methylsuccinate. the reaction is stirred at ambient temperature for 88 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 16 g, 0.40 mol) in anhydrous toluene (200 mL), a solution of 4-chloro-benzaldehyde (28 g, 0.20 mol) and 2-methyl-succinic acid dimethyl ester (48 g, 0.30 mol) in anhydrous toluene (100 mL) was added dropwise at room temperature under a stream of nitrogen. After being stirred at room temperature for 2 hours, the resulting mixture was diluted by adding 2 N sodium hydroxide (200 mL) dropwise, then heated to 80° C., and stirred at the same temperature for 2 hours. After being cooled to room temperature naturally, the aqueous layer was separated, washed with ethyl acetate (100 mL×3), then acidified with 2 N hydrochloric acid to pH 2, and extracted with ethyl acetate (150 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was precipitated from ethyl acetate/petroleum ether (10:1) to give 2-(4-chloro-benzylidene)-3-methyl-succinic acid (13.4 g, 26%) as a yellow solid. the resulting mixture was diluted heated to 80° C. stirred at the same temperature for 2 hours After being cooled to room temperature naturally the aqueous layer was separated washed with ethyl acetate (100 mL×3) extracted with ethyl acetate (150 mL×3) The combined organic layers were dried over sodium sulfate concentrated in vacuo The residue was precipitated from ethyl acetate/petroleum ether (10:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 20 g, 0.5 mol) in anhydrous toluene (200 mL), a solution of 4-fluoro-benzaldehyde (31 g, 0.25 mol) and 2-methyl-succinic acid dimethyl ester (60 g, 0.38 mol) in anhydrous toluene (100 mL) was added at room temperature under a stream of nitrogen. The resulting mixture was stirred at room temperature for 30 minutes and then quenched by the slow addition of water (20 mL). The mixture was acidified by the addition of concentrated hydrochloric acid, and extracted with ethyl acetate (200 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester (20 g, 33%) as a white solid. 1H NMR (400 MHz, acetone-d6) δ ppm 7.77 (s, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 3.82 (q, 7.2 Hz, 1H), 1.40 (d, J=6.8 Hz, 3H). quenched by the slow addition of water (20 mL) The mixture was acidified by the addition of concentrated hydrochloric acid extracted with ethyl acetate (200 mL×3) The combined organic layers were dried over sodium sulfate concentrated in vacuo The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure in Example 3 (3) was repeated to proceed with heating stirring reaction except that in place of 180 g of methyl formate and 96 g of methanol, 200 g of methanol was charged in the autoclave and carbon monoxide was pressurized into the autoclave so as to maintain the internal pressure at 40 kg/cm2G. After the temperature of the content in the autoclave reached 60° C., carbon monoxide was fed in the autoclave so as to maintain the internal pressure at 40 kg/cm2G to proceed with the reaction for 3 hours. Subsequently, the content therein was cooled, internal pressure was gradually lowered to atmospheric pressure, and the reaction product was taken out. As a result of analysis therefor, the conversion of methyl 3-carbamoylisobutyrate was 81.4% and there were obtained dimethyl methylsuccinate at a selectivity of 95.7% and formamide at a selectivity of 94.4%, each based on the reacted methyl 3-carbamoylisobutyrate. with heating to maintain the internal pressure at 40 kg/cm2G reached 60° C. to maintain the internal pressure at 40 kg/cm2G to proceed with the reaction for 3 hours Subsequently, the content therein was cooled As a result of analysis

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A one L stainless steel-made autoclave equipped with a stirrer was charged with 72.5 g of the methyl 3-carbamoylisobutyrate which had been obtained in the preceding item (2), 180 g of methyl formate, 96 g of methanol and 1.1 g of sodium methylate to proceed with heating reaction at 60° C. for 2 hours. The reaction product was cooled and then analyzed. As a result, the conversion of the methyl 3-carbamoylisobutyrate was 83.2% and, there were obtained dimethyl methylsuccinate at a selectivity of 99.8% based on the reacted methyl 3-carbamoylisobutyrate, and formamide at a selectivity of 98.4% based on the same. The sodium methylate in the reaction liquid was neutralized with sulfuric acid, and subsequently the reaction liquid was distilled by a conventional method. As a result, methyl formate and methanol were recovered and there were obtained 60 g of dimethyl methylsuccinate with at least 99% purity and 16 g of formamide with 99% purity. The recovery of these substances inclusive of an intermediate fraction was quantitative, respectively. subsequently the reaction liquid was distilled by a conventional method As a result, methyl formate and methanol were recovered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure in Example 1 was repeated to proceed with reaction except that in the second step of esterification, methanol in an amount by weight of 2.6 times that of the methyl 3-cyanoisobutyrate was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the reflux of methanol over a period of 5 hours; then at least 90% of water which was formed by the by-production of ether was removed outside the reaction system together with methanol; and additional methanol in an amount of 2.6 times that of the methyl 3-cyanoisobutyrate was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the reflux of methoanol over a period of 5 hours. As a result, dimethyl methylsuccinate was obtained at a yield of 97.6 mol % based on the fed methyl 3-cyanoisobutyrate, and by-production of dimethyl ether was at most 1 mol % based on the dimethyl methylsuccinate thus formed. was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the was removed outside the reaction system together with methanol and additional methanol in an amount of 2.6 times that of the methyl 3-cyanoisobutyrate was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the reflux of methoanol over a period of 5 hours