1-benzofuran-3-one

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

Procedure: A solution of 3-coumaranone (5.0 g, 37 mmol) and methyl(triphenylphosphoranylideneacetate) (13.5 g, 40 mmol) in toluene (70 mL) was heated to reflux for 25 hours. More toluene was added (50 mL), and after a further 5 hours, more methyl(triphenylphosphoranylideneacetate) (0.5 g, 1.5 mmol). After another 19 hours, a further 1.0 g (3.0 mmol) was added, and after a further 21 hours, the solvent was removed in vacuo. Column chromatography (heptane:ethyl acetate 4:1) gave the product as a brown oil, 33 mmol, 89%. to reflux for 25 hours After another 19 hours a further 1.0 g (3.0 mmol) was added after a further 21 hours the solvent was removed in vacuo

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

Procedure: To a stirred mixture of hexane washed sodium hydride (2.21 g, 0.046 mol, 50%/mineral oil) in THF (125 mL), was added diethyl cyanomethylphosphonate (8.15 g, 0.046 mol) dropwise. The reaction was stirred at room temperature for 1/2 hour, 3-coumaranone (sublimed) (5.6 g, 0.042 mol) in THF (100 mL) was added dropwise at 0° C., and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with water (300 mL), and extracted with ether (800 mL). The extracts were washed with brine (2×100 mL), dried (MgSO4), and concentrated to yield 6.67 g (100%) of the product as an off-white solid. the reaction mixture was stirred at room temperature overnight extracted with ether (800 mL) The extracts were washed with brine (2×100 mL) dried (MgSO4) concentrated

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

Procedure: A solution of 3-coumaranone (5.0 g, 37 mmol) and methyl(triphenylphosphoranylideneacetate) (13.5 g, 40 mmol) in toluene (70 mL) was heated to reflux for 25 hours. More toluene was added (50 mL), and after a further 5 hours, more methyl(triphenylphosphoranylideneacetate) (0.5 g, 1.5 mmol). After another 19 hours, a further 1.0 g (3.0 mmol) was added, and after a further 21 hours, the solvent was removed in vacuo. Column chromatography (heptane:ethyl acetate 4:1) gave the product as a brown oil, 33 mmol, 89%. to reflux for 25 hours After another 19 hours a further 1.0 g (3.0 mmol) was added after a further 21 hours the solvent was removed in vacuo

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

Procedure: A solution of 3-coumaranone (5.0 g, 37 mmol) and methyl(triphenylphosphoranylideneacetate) (13.5 g, 40 mmol) in toluene (70 mL) was heated to reflux for 25 hours. More toluene was added (50 mL), and after a further 5 hours, more methyl(triphenylphosphoranylideneacetate) (0.5 g, 1.5 mmol). After another 19 hours, a further 1.0 g (3.0 mmol) was added, and after a further 21 hours, the solvent was removed in vacuo. Column chromatography (heptane:ethyl acetate 4:1) gave the product as a brown oil, 33 mmol, 89%. to reflux for 25 hours After another 19 hours a further 1.0 g (3.0 mmol) was added after a further 21 hours the solvent was removed in vacuo

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

Procedure: KOtBu (0.673 g, 6 mmol) was dissolved in dry DMF (10 ml) with exclusion of oxygen. Phosphonoacetic acid triethyl ester (0.87 ml, 6 mmol) was then added to the mixture. After 20 min a solution of benzofuran-3(2H)-one (0.536 g, 4 mmol) in dry DMF (10 ml, argon atmosphere) was added to this mixture. The reaction mixture was stirred at room temperature for 1 h and thereafter poured on to ice (50 ml) for working up. The mixture obtained was extracted with diethyl ether (4×20 ml). The organic phase was washed with water (4×20 ml), dried with Na2SO4 and then concentrated. The product formed was purified by column chromatography [silica gel 60 (50 g); cyclohexane, ethyl acetate (4:1)] and obtained in a yield of 0.372 g (48%) as a yellowish oil. The mixture obtained was extracted with diethyl ether (4×20 ml) The organic phase was washed with water (4×20 ml) dried with Na2SO4 concentrated The product formed was purified by column chromatography [silica gel 60 (50 g); cyclohexane, ethyl acetate (4:1)] obtained in a yield of 0.372 g (48%) as a yellowish oil

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

Procedure: KOtBu (0.673 g, 6 mmol) was dissolved in dry DMF (10 ml) with exclusion of oxygen. Phosphonoacetic acid triethyl ester (0.87 ml, 6 mmol) was then added to the mixture. After 20 min a solution of benzofuran-3(2H)-one (0.536 g, 4 mmol) in dry DMF (10 ml, argon atmosphere) was added to this mixture. The reaction mixture was stirred at room temperature for 1 h and thereafter poured on to ice (50 ml) for working up. The mixture obtained was extracted with diethyl ether (4×20 ml). The organic phase was washed with water (4×20 ml), dried with Na2SO4 and then concentrated. The product formed was purified by column chromatography [silica gel 60 (50 g); cyclohexane, ethyl acetate (4:1)] and obtained in a yield of 0.372 g (48%) as a yellowish oil. The mixture obtained was extracted with diethyl ether (4×20 ml) The organic phase was washed with water (4×20 ml) dried with Na2SO4 concentrated The product formed was purified by column chromatography [silica gel 60 (50 g); cyclohexane, ethyl acetate (4:1)] obtained in a yield of 0.372 g (48%) as a yellowish oil

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2.64 gms (0.11 mole) of oil free sodium hydride in 200 ml of tetrahydrofuran (THF) was added dropwise a solution of 19.47 gms (0.11 mole) of diethylcyanomethylphosphonate in 75 mL of THF. After the H2 evolution had ceased, a solution of 13.4 g (0.1 mole) of 3-(2H)-benzo[b]furanone in 100 mL of THF was added. The solution was heated at 70° C. for 1.5 hours, cooled, and poured into 500 mL of 5% HCl, and washed with ether. The ether phase was washed with brine, dried (MgSO4), filtered and concentrated to give 15.4 g of a dark oil. The product was distilled at 96°-100° C./0.075 mm Hg to give 10.85 g of a yellow oil which crystallized upon standing. cooled washed with ether The ether phase was washed with brine dried (MgSO4) filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2.64 gms (0.11 mole) of oil free sodium hydride in 200 ml of tetrahydrofuran (THF) was added dropwise a solution of 19.47 gms (0.11 mole) of diethylcyanomethylphosphonate in 75 mL of THF. After the H2 evolution had ceased, a solution of 13.4 g (0.1 mole) of 3-(2H)-benzo[b]furanone in 100 mL of THF was added. The solution was heated at 70° C. for 1.5 hours, cooled, and poured into 500 mL of 5% HCl, and washed with ether. The ether phase was washed with brine, dried (MgSO4), filtered and concentrated to give 15.4 g of a dark oil. The product was distilled at 96°-100° C./0.075 mm Hg to give 10.85 g of a yellow oil which crystallized upon standing. cooled washed with ether The ether phase was washed with brine dried (MgSO4) filtered concentrated

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

Procedure: Ethyl trifluoroacetate (1.90 g, 14 mmol) was dissolved in ether (15 mL) and treated with sodium methoxide (25%) (3.67 g, 17 mmol). To the stirred solution was added 3-coumaranone (1.50 g, 11 mmol). The reaction was stirred at room temperature overnight (19 hours) and treated with 3N HCl (8 mL). The organic layer was collected, washed with brine, dried over MgSO4, and concentrated in vacuo to give a reddish brown solid (2.19 g, 85%): mp 108°-111° C.; 1H NMR (CDCl3) 300 MHz 7.84 (d, J=8.1 Hz, 1H) 7.66 (m, 1H) 7.52 (d, J=8.7 Hz, 1H) 7.37 (m, 1H). Mass spectrum: M+H=231. The organic layer was collected washed with brine dried over MgSO4 concentrated in vacuo

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

Procedure: Ethyl trifluoroacetate (1.90 g, 14 mmol) was dissolved in ether (15 mL) and treated with sodium methoxide (25%) (3.67 g, 17 mmol). To the stirred solution was added 3-coumaranone (1.50 g, 11 mmol). The reaction was stirred at room temperature overnight (19 hours) and treated with 3N HCl (8 mL). The organic layer was collected, washed with brine, dried over MgSO4, and concentrated in vacuo to give a reddish brown solid (2.19 g, 85%): mp 108°-111° C.; 1H NMR (CDCl3) 300 MHz 7.84 (d, J=8.1 Hz, 1H) 7.66 (m, 1H) 7.52 (d, J=8.7 Hz, 1H) 7.37 (m, 1H). Mass spectrum: M+H=231. The organic layer was collected washed with brine dried over MgSO4 concentrated in vacuo

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

Procedure: To a solution of benzofuran-3(2H)-one (9) (100 g, 0.745 mol) in methanol (700 mL) was added O-methyl hydroxylamine hydrochloride (68.5 g, 0.820 mol) and NaOAc (67.3 g, 0.820 mol) at ambient temperature followed by heating to reflux for 1-3 h. The progress of the reaction was monitored by the HPLC analysis. Upon completion of the reaction, the inorganics were filtered off, and methanol was recovered from the filtrate to provide residue. The residue was subjected to extractive work-up using dichloromethane (500 mL) and water (1 L) followed by recovery of the organic layer to obtain the product meeting the desired specifications. Yield—75-83%. by heating to reflux for 1-3 h Upon completion of the reaction the inorganics were filtered off methanol was recovered from the filtrate to provide residue to obtain the product

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

Procedure: To a solution of benzofuran-3-yl acetate (8) (100 g, 1.42 mol) in methanol (350 mL) was added diluted (7.5%) H2SO4 (500 mL) at ambient temperature followed by heating to reflux for 1-3 h. The progress of the reaction was monitored by HPLC analysis. Upon completion of the reaction, the reaction mixture was cooled, filtered, and the slurry was washed with water, and vacuum dried to obtain the product meeting the desired specifications. Yield—83-100%. by heating to reflux for 1-3 h Upon completion of the reaction the reaction mixture was cooled filtered the slurry was washed with water, and vacuum dried to obtain the product