6,7-dihydro-5H-1-benzofuran-4-one

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: A solution of 6,7-dihydro-4(5H)-benzofuranone (0.10 g, 0.73 mmol), carbon disulfide (0.048 mL, 0.80 mmol), and iodomethane (0.10 mL, 1.6 mmol) in tetrahydrofuran (1.8 mL) was treated with a 60% dispersion of sodium hydride in mineral oil (0.070 g, 1.8 mmol), stirred over night at ambient temperature and partitioned between saturated ammonium chloride and ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate), filtered and concentrated. The residue was treated with guanidine nitrate (0.36 g, 2.9 mmol), treated with 1.46 mL (2.2 mol) of 1.5 M sodium ethoxide in ethanol, heated to 80° C. overnight, cooled, diluted with water and extracted with dichloromethane (3×). The combined dichloromethane layers were dried (magnesium sulfate), filtered, concentrated and chromatographed using ethyl acetate in dichloromethane to provide the title compound: 1H NMR (300 MHz, CDCl3) δ 2.52 (s, 3H), 2.88-3.02 (m, 4H), 5.07 (br s, 2H), 6.87 (d, J=1.7 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 234 (M+H)+. partitioned between saturated ammonium chloride and ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) filtered concentrated heated to 80° C. overnight cooled extracted with dichloromethane (3×) The combined dichloromethane layers were dried (magnesium sulfate) filtered concentrated chromatographed

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

Procedure: To a solution of 11.1 g (0.0939 mol) of benzofuran in 150 ml of ether cooled to -20° C. was added a solution of 9.39 ml (0.0939 mol) 10M n-butyllithium in hexane, and the mixture was allowed to warm to 0° C. and stirred for 30 min. The mixture was cooled to -78° C. and 10.6 g (0.078 mol) of 4,5,6,7-tetrahydrobenzofuran-4-one in 20 ml of ether was added dropwise and the mixture was allowed to warm to room temperature, and then stirred for 1 h. To the mixture was added saturated ammonium chloride solution and the resulting mixture was extracted with ethyl acetate (3×100 ml). The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 19.3 g (97%) of 4,5,6,7-tetrahydro-4-(2-benzofuryl)benzofuran-7-ol, an oil which crystallized on standing as a yellow solid. The mixture was cooled to -78° C. to warm to room temperature stirred for 1 h the resulting mixture was extracted with ethyl acetate (3×100 ml) The organic layer was washed with brine dried over sodium sulfate concentrated in vacuo

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.4 g of 2,3-dihydroxypropylamine were added to a solution of 13.6 g of 4-oxo-4,5,6,7-tetrahydrobenzofuran in 200 cm3 of ethanol. The reaction medium was heated at 150° C. for 9 hours. After evaporation of the solvent and purification of the crude product on silica gel (ethyl acetate/methanol=9/1 ), 11.2 g of 4-oxo-4,5,6,7-tetrahydro-1-N-(β,γ-dihydroxypropyl)indole were recovered in the form of an oil. After evaporation of the solvent and purification of the crude product on silica gel (ethyl acetate/methanol=9/1 ), 11.2 g of 4-oxo-4,5,6,7-tetrahydro-1-N-(β,γ-dihydroxypropyl)indole were recovered in the form of an oil

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 80 g of ethanolamine were added to a solution of 136 g of 4-oxo-4,5,6,7-tetrahydrobenzofuran in 250 cm3 of ethanol. The solution was heated at 130° C. for 6 hours. After allowing the reaction mixture to return to room temperature with stirring, the mixture was poured over a mixture of 800 cm3 of isopropyl ether and 200 cm3 of petroleum ether. A product crystallized with stirring, and then it was drained, washed with petroleum ether and dried under vacuum over phosphorus pentoxide. 160 g of the expected product was recovered, which product was recrystallized from 240 cm3 of isopropanol. 150 g of the expected product was obtained whose melting point ranged from 96° to 97° C. to return to room temperature A product crystallized with stirring washed with petroleum ether dried under vacuum over phosphorus pentoxide 160 g of the expected product was recovered which product was recrystallized from 240 cm3 of isopropanol

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

Procedure: To a mixture of 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan (20.06 g) and THF (200 ml) was added dropwise 2M n-butylmagnesium bromide with ice-water cooling over 15 minutes. The mixture was stirred at r.t. overnight. The reaction mixture was poured into a mixture of a saturated aqueous solution of NH4Cl and AcOEt. The separated organic layer was washed with water and brine, and dried over MgSO4, and evaporated. The resulting oil was purified by chromatography on SiO2 (CHCl3 as eluent) to give 4-n-butylidene-4,5,6,7-tetrahydrobenzo[b]furan as a yellow oil (12.06 g). The separated organic layer was washed with water and brine dried over MgSO4 evaporated The resulting oil was purified by chromatography on SiO2 (CHCl3 as eluent)

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

Procedure: To a mixture of 3 ml of ethanol and 7 ml of 29% aqueous ammonia was added 1.0 g of 4-oxo-4,5,6,7-tetrahydrobenzofuran, and then the mixture was subjected to reaction in a sealed tube at 150° C. for 12 hours. After completing the reaction, the reaction mixture was concentrated. The resulting residue was applied to a column of silica gel and eluted with a mixed solvent of acetone and ethyl acetate to give 950 mg (yield: 96%) of 4-oxo-4,5,6,7-tetrahydroindole being a light yellowish crystal. the mixture was subjected to reaction in a sealed tube at 150° C. for 12 hours the reaction the reaction mixture was concentrated eluted with a mixed solvent of acetone and ethyl acetate

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

Procedure: To a mixture of 3 ml of ethanol and 7 ml of 29% aqueous ammonia was added 1.0 g of 4-oxo-4,5,6,7-tetrahydrobenzofuran, and then the mixture was subjected to reaction in a sealed tube at 150° C. for 12 hours. After completing the reaction, the reaction mixture was concentrated. The resulting residue was applied to a column of silica gel and eluted with a mixed solvent of acetone and ethyl acetate to give 950 mg (yield: 96%) of 4-oxo-4,5,6,7-tetrahydroindole being a light yellowish crystal. the mixture was subjected to reaction in a sealed tube at 150° C. for 12 hours the reaction the reaction mixture was concentrated eluted with a mixed solvent of acetone and ethyl acetate

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

Procedure: To a mixture of 10 ml of ethyl acetate, 2 ml of 40% aqueous solution of chloroacetaldehyde and about 3 ml of water was added 1.0 g (12 mmoles) of sodium hydrogencarbonate while cooling with ice, and then the resulting mixture was stirred. To the reaction mixture was added dropwise 5 ml of aqueous solution containing 1.12 g of 1,3-cyclohexanedione while cooling with ice at a rate of 0.05 ml/minute. The reaction mixture was maintained at a pH of from 6.2 to 8.7 throughout the reaction. After completing the dropping, the reaction mixture was stirred at a room temperature overnight, and then acidified with sulfuric acid. After stirring the mixture for one hour, the ethyl acetate layer was separated, washed with an aqueous solution of potassium carbonate for removing the unreacted 1,3-cyclohexanedione, and then dried on magnesium sulfate. After distilling away the solvent, the residue was applied to a column of silica gel and eluted with dichloromethane to give 1.09 g (yield: 80%) of 4-oxo-4,5,6,7-tetrahydrobenzofuran. while cooling with ice while cooling with ice at a rate of 0.05 ml/minute The reaction mixture was maintained at a pH of from 6.2 to 8.7 throughout the reaction was stirred at a room temperature overnight After stirring the mixture for one hour the ethyl acetate layer was separated washed with an aqueous solution of potassium carbonate for removing the unreacted 1,3-cyclohexanedione dried on magnesium sulfate After distilling away the solvent eluted with dichloromethane

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

Procedure: To a mixture of 10 ml of ethyl acetate, 2 ml of 40% aqueous solution of chloroacetaldehyde and about 3 ml of water was added 1.0 g (12 mmoles) of sodium hydrogencarbonate while cooling with ice, and then the resulting mixture was stirred. To the reaction mixture was added dropwise 5 ml of aqueous solution containing 1.12 g of 1,3-cyclohexanedione while cooling with ice at a rate of 0.05 ml/minute. The reaction mixture was maintained at a pH of from 6.2 to 8.7 throughout the reaction. After completing the dropping, the reaction mixture was stirred at a room temperature overnight, and then acidified with sulfuric acid. After stirring the mixture for one hour, the ethyl acetate layer was separated, washed with an aqueous solution of potassium carbonate for removing the unreacted 1,3-cyclohexanedione, and then dried on magnesium sulfate. After distilling away the solvent, the residue was applied to a column of silica gel and eluted with dichloromethane to give 1.09 g (yield: 80%) of 4-oxo-4,5,6,7-tetrahydrobenzofuran. while cooling with ice while cooling with ice at a rate of 0.05 ml/minute The reaction mixture was maintained at a pH of from 6.2 to 8.7 throughout the reaction was stirred at a room temperature overnight After stirring the mixture for one hour the ethyl acetate layer was separated washed with an aqueous solution of potassium carbonate for removing the unreacted 1,3-cyclohexanedione dried on magnesium sulfate After distilling away the solvent eluted with dichloromethane

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

Procedure: To a mixture of 80 ml of water and 20 ml of 40% aqueous solution of chloroacetaldehyde was added 10.0 g (119 mmoles) of sodium hydrogencarbonate while cooling with ice. To the resulting reaction mixture was added dropwise 90 ml of aqueous solution containing 11.2 g (100 mmoles) of 1,3-cyclohexanedione while cooling with ice at a rate of 0.4 ml/minute. The reaction mixture was maintained at a pH of from 9 to 6 throughout the reaction. After completing the dropping, the reaction mixture was stirred at a room temperature overnight. To the resulting reaction mixture was added about 100 ml of ethyl acetate, and then the reaction mixture was acidified (pH<1) with sulfuric acid and stirred for about one hour. The ethyl acetate layer was separated, washed with an aqueous solution of potassium carbonate, and dried on magnesium sulfate. After distilling away the ethyl acetate, the obtained residue was distilled under a reduced pressure to give 10.3 g (yield: 76%) of 4-oxo-4,5,6,7 -tetrahydrobenzofuran being a colorless oily material (boiling point: 66° C./1 torr). while cooling with ice To the resulting reaction mixture while cooling with ice at a rate of 0.4 ml/minute The reaction mixture was maintained at a pH of from 9 to 6 throughout the reaction To the resulting reaction mixture stirred for about one hour The ethyl acetate layer was separated washed with an aqueous solution of potassium carbonate dried on magnesium sulfate After distilling away the ethyl acetate the obtained residue was distilled under a reduced pressure