ethyl 4-(1,3-dioxoisoindol-2-yl)-3-oxobutanoate

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: To a solution of 2-(1,3-dioxoisoindolin-2-yl)acetic acid (3.01 g, 14.67 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (2.23 g, 15.47 mmol) and 4-dimethylaminopyridine (2.73 g, 22.35 mmol) in dichloromethane (150 mL) was added a solution of DCC (3.36 g, 16.28 mmol) in DCM (50 mL) at 0° C. The mixture was stirred at RT for 16 h. The insoluble materials were filtered off, and the filtrate was washed with 5% NaHSO4 aqueous solution. The organic phase was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was treated with EtOH (200 mL) and the resulting mixture was stirred at 70° C. for 4 h and then concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with EtOAc. The organic layers were washed with water and brine, dried over anhydrous MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with IPE to give the title compound as a colorless solid (3.43 g, 85%). 1H NMR (400 MHz, CDCl3) δ ppm 1.31 (t, J=6.8 Hz, 3H), 3.58 (s, 2H), 4.24 (q, J=6.8 Hz, 2H), 4.67 (s, 2H), 7.73-7.78 (m, 2H), 7.86-7.91 (m, 2H). The insoluble materials were filtered off the filtrate was washed with 5% NaHSO4 aqueous solution The organic phase was dried over anhydrous Na2SO4 filtered the filtrate was concentrated under reduced pressure The residue was treated with EtOH (200 mL) the resulting mixture was stirred at 70° C. for 4 h concentrated under reduced pressure Water was added to the residue the mixture was extracted with EtOAc The organic layers were washed with water and brine dried over anhydrous MgSO4 filtered The filtrate was concentrated under reduced pressure the residue was washed with IPE

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

実験手順: To a solution of 2-(1,3-dioxoisoindolin-2-yl)acetic acid (3.01 g, 14.67 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (2.23 g, 15.47 mmol) and 4-dimethylaminopyridine (2.73 g, 22.35 mmol) in dichloromethane (150 mL) was added a solution of DCC (3.36 g, 16.28 mmol) in DCM (50 mL) at 0° C. The mixture was stirred at RT for 16 h. The insoluble materials were filtered off, and the filtrate was washed with 5% NaHSO4 aqueous solution. The organic phase was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was treated with EtOH (200 mL) and the resulting mixture was stirred at 70° C. for 4 h and then concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with EtOAc. The organic layers were washed with water and brine, dried over anhydrous MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with IPE to give the title compound as a colorless solid (3.43 g, 85%). 1H NMR (400 MHz, CDCl3) δ ppm 1.31 (t, J=6.8 Hz, 3H), 3.58 (s, 2H), 4.24 (q, J=6.8 Hz, 2H), 4.67 (s, 2H), 7.73-7.78 (m, 2H), 7.86-7.91 (m, 2H). The insoluble materials were filtered off the filtrate was washed with 5% NaHSO4 aqueous solution The organic phase was dried over anhydrous Na2SO4 filtered the filtrate was concentrated under reduced pressure The residue was treated with EtOH (200 mL) the resulting mixture was stirred at 70° C. for 4 h concentrated under reduced pressure Water was added to the residue the mixture was extracted with EtOAc The organic layers were washed with water and brine dried over anhydrous MgSO4 filtered The filtrate was concentrated under reduced pressure the residue was washed with IPE

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: The title compound was prepared in a manner analogous to Intermediate 124 starting from ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate (Intermediate 25) and sulfuryl chloride.

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

実験手順: The title compound was prepared in a manner analogous to Intermediate 124 starting from ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate (Intermediate 25) and sulfuryl chloride.

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

実験手順: The title compound was prepared in a manner analogous to Intermediate 123 starting from 2,2-dimethyl-1,3-dioxane-4,6-dione and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride.

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

実験手順: The title compound was prepared in a manner analogous to Intermediate 123 starting from 2,2-dimethyl-1,3-dioxane-4,6-dione and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride.

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

実験手順: The title compound was prepared in a manner analogous to Intermediate 123 starting from 2,2-dimethyl-1,3-dioxane-4,6-dione and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride.

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

実験手順: To a solution of 2-(1,3-dioxoisoindolin-2-yl)acetic acid (3.01 g, 14.67 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (2.23 g, 15.47 mmol) and 4-dimethylaminopyridine (2.73 g, 22.35 mmol) in dichloromethane (150 mL) was added a solution of DCC (3.36 g, 16.28 mmol) in DCM (50 mL) at 0° C. The mixture was stirred at RT for 16 h. The insoluble materials were filtered off, and the filtrate was washed with 5% NaHSO4 aqueous solution. The organic phase was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was treated with EtOH (200 mL) and the resulting mixture was stirred at 70° C. for 4 h and then concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with EtOAc. The organic layers were washed with water and brine, dried over anhydrous MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with IPE to give the title compound as a colorless solid (3.43 g, 85%). 1H NMR (400 MHz, CDCl3) δ ppm 1.31 (t, J=6.8 Hz, 3H,), 3.58 (s, 2H), 4.24 (q, J=6.8 Hz, 2H), 4.67 (s, 2H), 7.73-7.78 (m, 2H), 7.86-7.91 (m, 2H). The insoluble materials were filtered off the filtrate was washed with 5% NaHSO4 aqueous solution The organic phase was dried over anhydrous Na2SO4 filtered the filtrate was concentrated under reduced pressure The residue was treated with EtOH (200 mL) the resulting mixture was stirred at 70° C. for 4 h concentrated under reduced pressure Water was added to the residue the mixture was extracted with EtOAc The organic layers were washed with water and brine dried over anhydrous MgSO4 filtered The filtrate was concentrated under reduced pressure the residue was washed with IPE

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

実験手順: 13 g of 2-chlorobenzaldehyde, 28 g of phthalimidoacetoacetic acid ethyl ester and 13 g of β-aminocrotonic acid ethyl ester in 250 ccs of ethanol are heated to the boil under reflux for about 70 hours, the mixture is allowed to cool, whilst stirring, and after filtering, light yellow crystals of melting point 174°-176° C. are obtained; yield: 90%. under reflux for about 70 hours to cool after filtering light yellow crystals of melting point 174°-176° C. are obtained

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

実験手順: 7.5 g of 4-nitrobenzaldehyde, 28 g of γ-phthalimidoacetoacetic acid ethyl ester and 7 ccs of concentrated ammonia in 120 ccs of ethanol are heated to the boil under reflux for 60 hours and the product is filtered off after cooling on ice. under reflux for 60 hours the product is filtered off after cooling on ice