1-ethylpyrrolidin-2-one

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

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, N-ethyl-2-pyrrolidone (NMP) about 18 weight percent of solids, the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, and which mixture was stirred and subjected to ball milling with 2 millimeter stainless steel shots via an Attritor grinding mill for 18 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent dispersed in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion was filtered with a 20 micron Nylon cloth filter. More specifically, an intermediate transfer coating dispersion was prepared by providing grinding mill for 18 hours

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, N-ethyl-2-pyrrolidone (NMP) about 18 weight percent of solids, the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, and which mixture was stirred and subjected to ball milling with 2 millimeter stainless steel shots via an Attritor grinding mill for 18 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent dispersed in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion was filtered with a 20 micron Nylon cloth filter. More specifically, an intermediate transfer coating dispersion was prepared by providing grinding mill for 18 hours

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, the solvent N-ethyl-2-pyrrolidone (NMP), the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, about 18 weight percent of solids, and which mixture was stirred and subjected to ball milling with 2 millimeter stainless steel shots via an Attritor grinding mill for 18 hours at a speed of about 200 rpm for 48 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent contained in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion was filtered through a 20 micron Nylon cloth filter. More specifically, an intermediate transfer coating dispersion was prepared by providing grinding mill for 18 hours at a speed of about 200 rpm for 48 hours

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3 g of methyl 4-fluoro-2-methoxy-5-nitrobenzoate, 1.99 g of 2-(tetrahydro-2H-pyran-4-yl)-1H-imidazole, and 15 mL of N-ethylpyrrolidone was added 3.6 g of potassium carbonate, followed by stirring at 100° C. for 3 hours. To the reaction mixture were added water and ethyl acetate, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 4.12 g of methyl 2-methoxy-5-nitro-4-[2-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-1-yl]-benzoate. followed by extraction with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform/methanol)

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

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, the solvent N-ethyl-2-pyrrolidone (NMP), the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, about 18 weight percent of solids, and which mixture was subjected to mechanical stirring at a speed of about 200 rpm for 48 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent contained in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion could not be effectively filtered through a 20 micron Nylon cloth filter due to the very large particle sizes present in the dispersion. More specifically, an intermediate transfer coating dispersion was prepared by providing

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, a solvent of N-ethyl-2-pyrrolidone (NMP), the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, about 18 weight percent of solids, and which mixture was subjected to ball milling with 2 millimeters stainless steel shots via an Attritor grinding mill for 18 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent contained dispersed in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion was filtered through a 20 micron Nylon cloth filter. More specifically, an intermediate transfer coating dispersion was prepared by providing grinding mill for 18 hours

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

Procedure: More specifically, an intermediate transfer coating dispersion was prepared by providing a mixture of Special Carbon Black 4, available from Orion Chemicals, a solvent of N-ethyl-2-pyrrolidone (NMP), the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine, and the leveling agent NOVEC™ FC-4432, a fluoro surfactant available from 3M, about 18 weight percent of solids, and which mixture was subjected to ball milling with 2 millimeters stainless steel shots via an Attritor grinding mill for 18 hours. There resulted a coating dispersion of the polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent contained dispersed in NMP, where the weight ratio of polyamic acid of biphenyl tetracarboxylicdianhydride/phenylenediamine/carbon black/leveling agent was 88.8/11/0.2, and which dispersion was filtered through a 20 micron Nylon cloth filter. More specifically, an intermediate transfer coating dispersion was prepared by providing grinding mill for 18 hours

Conditions: temp:54.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of noroxymorphone (62 Kg), N-ethyl-2-pyrrolidinone (186 kg), cyclopropymethyl bromide (37.8 kg) and N,N-diisopropylethylamine (36.2 kg) was heated to 52-57° C. for 24 hours and 45 min. The mixture was then diluted with a solution prepared by mixing hydrochloric acid 37% (30 kg) and water (82 kg). Low boiling compounds were removed by distillation under vacuum keeping the temperature below 70° C. After cooling to 25-30° C. the mixture was further diluted with water (1975 kg). Ammonium hydroxide 4% (206 kg) was then added over three hours till pH=9-10 to precipitate the product. The solid was filtered, washed with water (2×124 kg) and dried under vacuum at 60° C. obtaining 71.3 kg of naltrexone (molar yield 89.6%). HPLC analysis (% by area): naltrexone 99.45%, noroxymorphone 0.16%, 3-cyclopropylmethylnaltrexone 0.28% The mixture was then diluted with a solution prepared were removed by distillation under vacuum the temperature below 70° C After cooling to 25-30° C. the mixture was further diluted with water (1975 kg) Ammonium hydroxide 4% (206 kg) was then added over three hours till pH=9-10 to precipitate the product The solid was filtered washed with water (2×124 kg) dried under vacuum at 60° C.