4,7-dimethoxy-2-benzofuran-1,3-dione

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

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,6-Dimethoxybenzene-1,2-dicarboxylic acid (20 g) was dissolved in pyridine (100 ml) at room temperature. The solution was then cooled in a cold water bath and acetic anhydride (27 g, 25 ml) added dropwise over 10 minutes (temperature rose from 23° to 25° C.) The reaction mixture was then stirred for 90 minutes at 12° C., filtered, washed with ether (100 ml) and pulled dry to give a pale cream solid. Dried at 50° C. in a vacuum oven, m.p. 268°-269° C. The solution was then cooled in a cold water bath filtered washed with ether (100 ml) pulled dry to give a pale cream solid Dried at 50° C. in a vacuum oven, m.p. 268°-269° C.

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

Procedure: In a manner analogous to that described in Example 3(A), from 0.5 g of (aminomethyl)[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester acetate and 0.27 g of 3,6-dimethyoxyphthalic anhydride, there was obtained 0.325 g of [(3,6-dimethoxyphthalimido)methyl][(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester in the form of a pale yellow foam.

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

Procedure: To an ice-cold solution of 1.7 g. of sodium borohydride in 100 ml. of dimethylformide is added 9.2 g. of 3,6-dimethoxyphthalic anhydride. The cold bath is removed and the mixture stirred for one hour. The mixture is cooled in ice and 20 ml. of hydrochloric acid is slowly added. The solvent is removed in vacuo and the residue is slurried in 100 ml. of water. The resulting solid is filtered, dissolved in chloroform and dried. After removal of solvent, the solid is recrystallized from toluene to yield 4,7-dimethoxyphthalide with a melting point of 168°-170° C. of dimethylformide is added 9.2 g The cold bath is removed The mixture is cooled in ice of hydrochloric acid is slowly added The solvent is removed in vacuo The resulting solid is filtered dissolved in chloroform dried After removal of solvent the solid is recrystallized from toluene

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

Procedure: To an ice-cold solution of 1.7 g. of sodium borohydride in 100 ml. of dimethylformide is added 9.2 g. of 3,6-dimethoxyphthalic anhydride. The cold bath is removed and the mixture stirred for one hour. The mixture is cooled in ice and 20 ml. of hydrochloric acid is slowly added. The solvent is removed in vacuo and the residue is slurried in 100 ml. of water. The resulting solid is filtered, dissolved in chloroform and dried. After removal of solvent, the solid is recrystallized from toluene to yield 4,7-dimethoxyphthalide with a melting point of 168°-170° C. of dimethylformide is added 9.2 g The cold bath is removed The mixture is cooled in ice of hydrochloric acid is slowly added The solvent is removed in vacuo The resulting solid is filtered dissolved in chloroform dried After removal of solvent the solid is recrystallized from toluene

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,6-Dimethoxybenzene-1,2-dicarboxylic acid (20 g) was dissolved in pyridine (100 ml) at room temperature. The solution was then cooled in a cold water bath and acetic anhydride (27 g, 25 ml) added dropwise over 10 minutes (temperature rose from 23° to 25° C.) The reaction mixture was then stirred for 90 minutes at 12° C., filtered, washed with ether (100 ml) and pulled dry to give a pale cream solid. Dried at 50° C. in a vacuum oven, m.p. 268°-269° C. The solution was then cooled in a cold water bath filtered washed with ether (100 ml) pulled dry to give a pale cream solid Dried at 50° C. in a vacuum oven, m.p. 268°-269° C.

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,6-Dimethoxybenzene-1,2-dicarboxylic acid (20 g) was dissolved in pyridine (100 ml) at room temperature. The solution was then cooled in a cold water bath and acetic anhydride (27 g, 25 ml) added dropwise over 10 minutes (temperature rose from 23° to 25° C.) The reaction mixture was then stirred for 90 minutes at 12° C., filtered, washed with ether (100 ml) and pulled dry to give a pale cream solid. Dried at 50° C. in a vacuum oven, m.p. 268°-269° C. The solution was then cooled in a cold water bath filtered washed with ether (100 ml) pulled dry to give a pale cream solid Dried at 50° C. in a vacuum oven, m.p. 268°-269° C.

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

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

Procedure: In a manner analogous to that described in Example 3(A), from 0.5 g of (aminomethyl)[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester acetate and 0.27 g of 3,6-dimethyoxyphthalic anhydride, there was obtained 0.325 g of [(3,6-dimethoxyphthalimido)methyl][(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester in the form of a pale yellow foam.

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

Procedure: To an ice-cold solution of 1.7 g. of sodium borohydride in 100 ml. of dimethylformide is added 9.2 g. of 3,6-dimethoxyphthalic anhydride. The cold bath is removed and the mixture stirred for one hour. The mixture is cooled in ice and 20 ml. of hydrochloric acid is slowly added. The solvent is removed in vacuo and the residue is slurried in 100 ml. of water. The resulting solid is filtered, dissolved in chloroform and dried. After removal of solvent, the solid is recrystallized from toluene to yield 4,7-dimethoxyphthalide with a melting point of 168°-170° C. of dimethylformide is added 9.2 g The cold bath is removed The mixture is cooled in ice of hydrochloric acid is slowly added The solvent is removed in vacuo The resulting solid is filtered dissolved in chloroform dried After removal of solvent the solid is recrystallized from toluene

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,6-Dimethoxybenzene-1,2-dicarboxylic acid (20 g) was dissolved in pyridine (100 ml) at room temperature. The solution was then cooled in a cold water bath and acetic anhydride (27 g, 25 ml) added dropwise over 10 minutes (temperature rose from 23° to 25° C.) The reaction mixture was then stirred for 90 minutes at 12° C., filtered, washed with ether (100 ml) and pulled dry to give a pale cream solid. Dried at 50° C. in a vacuum oven, m.p. 268°-269° C. The solution was then cooled in a cold water bath filtered washed with ether (100 ml) pulled dry to give a pale cream solid Dried at 50° C. in a vacuum oven, m.p. 268°-269° C.