2-(4,4-diethoxybutyl)isoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A 10.0 g sample of 2-chlorophenylhydrazine hydrochloride and 17.9 g of 4-phthalimidobutyraldehyde diethyl acetal were stirred in 200 mL ethanol with 1 mL 5N HCl. The mixture was concentrated to a residue which was slurried in a small amount of methylene chloride. A yellow solid was collected and vacuum dried at 40° C. The solid was stirred in 500 mL ethanol. Hydrazine hydrate (14 g) was added and the mixture was heated at reflux for 14 hours. A 60 mL sample of 5N HCl was added and the mixture was heated at reflux for 1 hour. The mixture was allowed to cool and was concentrated to a residue. The residue was partitioned between 1N NaOH and chloroform. The organic layer was separated and the aqueous layer was extracted with chloroform. The combined extracts were dried (Na2SO4) and concentrated to an oil. The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide. Fractions containing product were concentrated to an oil which was taken up in a small amount of methanol and added to ethereal HCl. A solid was collected, washed with diethyl ether, and vacuum dried at 50° C. The mixture was concentrated to a residue which A yellow solid was collected vacuum dried at 40° C Hydrazine hydrate (14 g) was added the mixture was heated at reflux for 14 hours A 60 mL sample of 5N HCl was added the mixture was heated at reflux for 1 hour to cool was concentrated to a residue The residue was partitioned between 1N NaOH and chloroform The organic layer was separated the aqueous layer was extracted with chloroform The combined extracts were dried (Na2SO4) concentrated to an oil The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide Fractions containing product were concentrated to an oil which added to ethereal HCl A solid was collected washed with diethyl ether, and vacuum dried at 50° C.

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

Procedure: A solution of 4-phthalimidobutyraldehyde diethyl acetal (125 g, 0.43 mol) in a 1:1 mixture of tetrahydrofuran and 2N hydrochloric acid (800 ml) was heated at reflux for 0.75 h. The mixture was cooled, concentrated to 400 ml and extracted into dichloromethane (3×200 ml). Combined organics were dried (Na2SO4) and evaporated in vacuo to afford the title compound as a brown oil that solidified on standing (95 g, 100%). was heated at reflux for 0.75 h The mixture was cooled concentrated to 400 ml extracted into dichloromethane (3×200 ml) Combined organics were dried (Na2SO4) evaporated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-aminobutyraldehyde diethyl acetal (48.5 g, 0.3 mol) in tetrahydrofuran (60 ml) was added dropwise to a stirred slurry of N-(ethoxycarbonyl) phthalimide (65.93 g, 0.3 mol) in tetrahydrofuran (250 ml) at 0° C. After stirring at 0° C. for 0.16 h and at room temperature for 18 h the solvent was removed in vacuo and the residue distilled at 1 mmHg to remove the ethyl carbamate by-product. The residual brown oil was allowed to cool to afford the title compound (91 g, 93%). was removed in vacuo the residue distilled at 1 mmHg to remove the ethyl carbamate by-product to cool

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

Procedure: A 10.0 g sample of 2-chlorophenylhydrazine hydrochloride and 17.9 g of 4-phthalimidobutyraldehyde diethyl acetal were stirred in 200 mL ethanol with 1 mL 5N HCl. The mixture was concentrated to a residue which was slurried in a small amount of methylene chloride. A yellow solid was collected and vacuum dried at 40° C. The solid was stirred in 500 mL ethanol. Hydrazine hydrate (14 g) was added and the mixture was heated at reflux for 14 hours. A 60 mL sample of 5N HCl was added and the mixture was heated at reflux for 1 hour. The mixture was allowed to cool and was concentrated to a residue. The residue was partitioned between 1N NaOH and chloroform. The organic layer was separated and the aqueous layer was extracted with chloroform. The combined extracts were dried (Na2 SO4) and concentrated to an oil. The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide. Fractions containing product were concentrated to an oil which was taken up in a small amount of methanol and added to ethereal HCl. A solid was collected, washed with diethyl ether, and vacuum dried at 50° C. The mixture was concentrated to a residue which A yellow solid was collected vacuum dried at 40° C Hydrazine hydrate (14 g) was added the mixture was heated at reflux for 14 hours A 60 mL sample of 5N HCl was added the mixture was heated at reflux for 1 hour to cool was concentrated to a residue The residue was partitioned between 1N NaOH and chloroform The organic layer was separated the aqueous layer was extracted with chloroform The combined extracts were dried (Na2 SO4) concentrated to an oil The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide Fractions containing product were concentrated to an oil which added to ethereal HCl A solid was collected washed with diethyl ether, and vacuum dried at 50° C.

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

Procedure: Protect the amino function in 4,4-diethoxybutylamine by conversion thereof to a phthalimido function. Hydrolyze the resultant 1-phthalimido-4,4-diethoxybutane with 1N aqueous sulfuric acid at 25° C to obtain 4-phthalimidobutanal. Subject the compound to reductive amination using ammonium chloride and sodium cyanoborohydride in aqueous methanol at 25° C to obtain 4-phthalimidobutylamine. at 25° C

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

Procedure: Protect the amino function in 4,4-diethoxybutylamine by conversion thereof to a phthalimido function. Hydrolyze the resultant 1-phthalimido-4,4-diethoxybutane with 1N aqueous sulfuric acid at 25° C to obtain 4-phthalimidobutanal. Subject the compound to reductive amination using ammonium chloride and sodium cyanoborohydride in aqueous methanol at 25° C to obtain 4-phthalimidobutylamine. at 25° C

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

Procedure: A 10.0 g sample of 2-chlorophenylhydrazine hydrochloride and 17.9 g of 4-phthalimidobutyraldehyde diethyl acetal were stirred in 200 mL ethanol with 1 mL 5N HCl. The mixture was concentrated to a residue which was slurried in a small amount of methylene chloride. A yellow solid was collected and vacuum dried at 40° C. The solid was stirred in 500 mL ethanol. Hydrazine hydrate (14 g) was added and the mixture was heated at reflux for 14 hours. A 60 mL sample of 5N HCl was added and the mixture was heated at reflux for 1 hour. The mixture was allowed to cool and was concentrated to a residue. The residue was partitioned between 1N NaOH and chloroform. The organic layer was separated and the aqueous layer was extracted with chloroform. The combined extracts were dried (Na2SO4) and concentrated to an oil. The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide. Fractions containing product were concentrated to an oil which was taken up in a small amount of methanol and added to ethereal HCl. A solid was collected, washed with diethyl ether, and vacuum dried at 50° C. The mixture was concentrated to a residue which A yellow solid was collected vacuum dried at 40° C Hydrazine hydrate (14 g) was added the mixture was heated at reflux for 14 hours A 60 mL sample of 5N HCl was added the mixture was heated at reflux for 1 hour to cool was concentrated to a residue The residue was partitioned between 1N NaOH and chloroform The organic layer was separated the aqueous layer was extracted with chloroform The combined extracts were dried (Na2SO4) concentrated to an oil The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide Fractions containing product were concentrated to an oil which added to ethereal HCl A solid was collected washed with diethyl ether, and vacuum dried at 50° C.

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

Procedure: A 10.0 g sample of 2-chlorophenylhydrazine hydrochloride and 17.9 g of 4-phthalimidobutyraldehyde diethyl acetal were stirred in 200 mL ethanol with 1 mL 5N HCl. The mixture was concentrated to a residue which was slurried in a small amount of methylene chloride. A yellow solid was collected and vacuum dried at 40° C. The solid was stirred in 500 mL ethanol. Hydrazine hydrate (14 g) was added and the mixture was heated at reflux for 14 hours. A 60 mL sample of 5N HCl was added and the mixture was heated at reflux for 1 hour. The mixture was allowed to cool and was concentrated to a residue. The residue was partitioned between 1N NaOH and chloroform. The organic layer was separated and the aqueous layer was extracted with chloroform. The combined extracts were dried (Na2SO4) and concentrated to an oil. The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide. Fractions containing product were concentrated to an oil which was taken up in a small amount of methanol and added to ethereal HCl. A solid was collected, washed with diethyl ether, and vacuum dried at 50° C. The mixture was concentrated to a residue which A yellow solid was collected vacuum dried at 40° C Hydrazine hydrate (14 g) was added the mixture was heated at reflux for 14 hours A 60 mL sample of 5N HCl was added the mixture was heated at reflux for 1 hour to cool was concentrated to a residue The residue was partitioned between 1N NaOH and chloroform The organic layer was separated the aqueous layer was extracted with chloroform The combined extracts were dried (Na2SO4) concentrated to an oil The oil was chromatographed on silica gel using a gradient of 0-10% methanol in chloroform containing 0.2% ammonium hydroxide Fractions containing product were concentrated to an oil which added to ethereal HCl A solid was collected washed with diethyl ether, and vacuum dried at 50° C.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 4-hydrazino phenylacetonitrile hydrochloride (3.15 g) and 4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)butanal diethyl acetal (4.95 g) in acetic acid (25%, 150 ml) was refluxed for 2 h, cooled to 25°, precipitate filtered, washed with water (2×20 ml) and ether (100 ml). The crude product was obtained as a dark solid (4.5 g) which was triturated with ethyl acetate to give the title compound (3.16 g) m.p. 185°-186°. was refluxed for 2 h cooled to 25° precipitate filtered washed with water (2×20 ml) and ether (100 ml)

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

Procedure: A mixture of the crude 2-(4-hydrazinophenyl)acetamide hydrochloride (16.19 g) (contains 0.05 mol) and 4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)butanal diethyl acetal (14.5 g) was heated under reflux in 25% aqueous acetic acid (1 l) for 30 min. The cooled mixture was poured into ethyl acetate (750 ml) the organic phase was separated and the aqueous phase was washed with ethyl acetate (250 ml). The combined organic extracts were washed with water (500 ml), dried (Na2SO4) and evaporated under reduced pressure. Water (500 ml) was added to the oily residue which solidified on stirring. The solid was collected by filtration, washed with water and dried. Crystallisation from ethyl acetate-methanol gave the title compound as pale yellow granules (11.9 g) m.p. 191°-3° C. was heated was separated the aqueous phase was washed with ethyl acetate (250 ml) The combined organic extracts were washed with water (500 ml) dried (Na2SO4) evaporated under reduced pressure Water (500 ml) was added to the oily residue which The solid was collected by filtration washed with water dried Crystallisation from ethyl acetate-methanol