2-(1,3-dioxoisoindol-2-yl)acetyl chloride

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

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

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

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

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

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

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

Procedure: To a suspension of 3-amino-1-(tert-butyldiphenylsilyloxymethyl)-2,6-dimethylbenzene (42.4 g) in pyridine (17.2 g) and N,N-dimethylformamide (212 ml) was added phthalimidoacetyl chloride (25.6 g) over the period of 15 minutes under ice-cooling, and the mixture was stirred for 1 hour at the same temperature. Water was added thereto, and the resulting precipitate was collected by filtration and washed with acetone to give 1-(tert-butyldiphenylsilyloxymethyl)-2,6-dimethyl-3-(phthalimidoacetylamino)benzene (59.1 g) as colorless crystals. cooling the resulting precipitate was collected by filtration washed with acetone

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

Procedure: To a solution of (3aR*,10aS*)-9-[3-(benzyloxycarbonylamino)benzyl]-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one (1.9 g, 4.3 mmol) in 1,2-dichloroethane (50 mL) was added phthalimidoacetyl chloride (1.1 g, 4.7 mmol) at room temperature and the mixture was refluxed for 17 hours. After cooling, saturated aqueous NaHCO3 solution (30 mL) was added and the mixture was diluted with water and extracted with 2 portions of chloroform. The pooled organic layer was washed with saturated aqueous NaCl solution, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was crystallized from diethyl ether to provide 1.5 g (yield 55%) of the title compound. m.p. 224°-225° C. the mixture was refluxed for 17 hours After cooling extracted with 2 portions of chloroform The pooled organic layer was washed with saturated aqueous NaCl solution dried over MgSO4 filtered concentrated under reduced pressure The residue was crystallized from diethyl ether

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

Procedure: To a solution of (3aR*,10aS*)-9-(4-benzyloxybenzyl)-2,3,3a,4,9,10a-hexahydrobenzo[b ]cyclopenta[e][1,4]diazepin-10(1H)-one (3.1 g, 7.8 mmol) in 1,2-dichloroethane was added phthalimidoacetyl chloride (1.9 g, 8.5 mmol). The mixture was refluxed for 17 hours. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate. The aqueous layer was separated. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over magnesium sulfate and subjected to filtration. The filtrate was concentrated under reduced pressure. The concentrate was parified by silica-gel column chromatography (hexane-ethyl acetate 1:3), which was crystallized from diethyl ether to give the desired product (1.9 g, 42%), m.p.179°-181° C. The mixture was refluxed for 17 hours The aqueous layer was separated The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate dried over magnesium sulfate subjected to filtration The filtrate was concentrated under reduced pressure was crystallized from diethyl ether

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

Procedure: To a solution of Meldrum's acid (14.4 g, 0.10 mol) and pyridine (15.8 g, 0.20 mol) in dichloromethane (100 mL) was added dropwise at 0° C., taking 10 minutes, a solution of phthalimidoacetyl chloride (24.6 g,. 0.11 mol) in dichloromethane (50 mL). The mixture was stirred for 30 minutes at the same temperature and for 30 minutes at room temperature. To the reaction mixture was added 1N HCl (200 mL), then insoluble material was filtered off. The aqueous layer was separated, and the organic layer was washed with water, dried over magnesium sulfate and subjected to filtration. The filtrate was concentrated under reduced pressure. The concentrate was suspended in methanol (200 mL), which was refluxed for 1.5 hour. The reaction mixture was left standing for cooling. Crystalline precipitate was collected by filtration and washed with methanol to give the object compound (18.4 g, 70%), m.p.139°-140° C. insoluble material was filtered off The aqueous layer was separated the organic layer was washed with water dried over magnesium sulfate subjected to filtration The filtrate was concentrated under reduced pressure which was refluxed for 1.5 hour The reaction mixture was left for cooling Crystalline precipitate was collected by filtration washed with methanol

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

Procedure: A mixture of phthalimidoacetic acid (25.1 g, 0.122 mol) and thionyl chloride (50 mL) was heated for one hour under reflux. The reaction mixture was cooled and, then, concentrated under reduced pressure. The concentrate was recrystallized from dichloromethane-hexane to give 26.4 g (97%) the titled compound, which was used for the subsequent reaction without further purification. was heated for one hour under reflux The reaction mixture was cooled concentrated under reduced pressure The concentrate was recrystallized from dichloromethane-hexane

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

Procedure: To a suspension of 2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one (2.02 g, 10 mmol) in 1,2-dichloroethane (15 mL) was added phthalimidoacetyl chloride (2.24 g, 10 mmol),and the mixture was stirred for 15 minutes at room temperature. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate (10 mL) to give precipitate, which was filtered off. The aqueous layer of the filtrate was seperated. The organic layer was washed with water, dried over magnesium sulfate and subjected to filtration. The filtrate was concentrated under reduced pressure. The concentrate was combined with the precipitate filtered previously, which was washed with methanol, followed by recrystallization from chloroform-methanol to give 2.42 g (yield 62%) of a cis-trans mixture (3:2). m.p. 293°-294° C. to give precipitate, which was filtered off The aqueous layer of the filtrate was seperated The organic layer was washed with water dried over magnesium sulfate subjected to filtration The filtrate was concentrated under reduced pressure filtered previously which was washed with methanol followed by recrystallization from chloroform-methanol