N,N,N',N'-tetraethylethane-1,2-diamine

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

Procedure: The ability of trichlorosilane to redistribute in the presence of tetraethylethylenediamine (TEEDA) and methylene chloride to form a complex comprising dichlorosilane and TEEDA was evaluated. All reactions were performed in a glass flask under a blanket of dry nitrogen. Trichlorosilane was distilled before use. TEEDA was dried by refluxing over CaH2 and then distilled. Dichloromethane was distilled from P2O5 just prior to use. The volumes of materials placed in the flask are provided in Table 1. Materials were added to the flask through a rubber septum by means of a syringe.

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

Procedure: The ability of trichlorosilane to redistribute in the presence of tetraethylethylenediamine (TEEDA) and methylene chloride to form a complex comprising dichlorosilane and TEEDA was evaluated. All reactions were performed in a glass flask under a blanket of dry nitrogen. Trichlorosilane was distilled before use. TEEDA was dried by refluxing over CaH2 and then distilled. Dichloromethane was distilled from P2O5 just prior to use. The volumes of materials placed in the flask are provided in Table 1. Materials were added to the flask through a rubber septum by means of a syringe.

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

Procedure: To a mixture of tetrahydrofuran (45 ml) and tetraethylethylenediamine (1.5 ml) were successively added a 1.0M sodium hexamethyldisilazide--tetrahydrofuran solution (0.892 ml) and methyl acetate (71.2 μl) at -78° C. The mixture was stirred for 30 minutes, and then a tetrahydrofuran solution of (2S,4R)-N-tert-butoxycarbonyl-4-(tert-butyldimethylsiloxy)prolinal (196 mg) was added thereto. This solution was stirred for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction solution. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1) to obtain the title compound [209 mg, yield: 87.1%; (R)-isomer (polar compound):(S)-isomer (less polar compound)=1.82:1]. at -78° C This solution was stirred for 30 minutes The mixture was extracted with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent was removed in vacuo The residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1)

Conditions: temp:87.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 L flask was equipped with magnetic stirring bar, cooling bath (liquid nitrogen), stopcock connected to an ammonia cylinder and a vacuum system. The flask was charged with FeCl3 (0.1 g) and evacuated. Ammonium gas was condensed to give liquid ammonium (600 ml). Potassium (19.50 g 0.50 mole) was added in small pieces (each about 0.5 g) under an argon atmosphere. The solution initially became blue but became a grey suspension after heating at reflux for 30 min. Into the potassium amide/liquid ammonia suspension was added in small portions isoquinoline-7-carboxylic acid {ref F. T. Tyson, JACS, 1939,61,183} (17.0 g 0.10 mole). The free acid initially dissolved but the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h. After careful addition of tetraethylethylene diamine (TEEDA) (86 g 0.50 mole), toluene (170 ml) and 18-crown-6 (1 g) the ammonia was allowed to evaporate slowly over 40 h to give a new suspension of the isoquinoline-7-carboxylic acid potassium salt. The reaction mixture was heated to 87° C. for 48 h. A sample was removed and analysed by nmr which indicated that there was still some unreacted starting material present. Ammonia was bubbled through the reaction mixture for 2 h and nmr analysis then revealed that no starting material remained. The reaction was then cooled to −16° C., ice (200 g) was added to destroy excess potassium amide and all solvents evaporated at 76° C. and 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which was dissolved in water (1.2 L) and filtered through Celite to give a clear solution. This was acidified to pH 7 by addition of acetic acid (34 g) and allowed to stand overnight. The precipitate was collected by filtration, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder. The crude product (17.6 g) was dissolved in water (4 L), and concentrated HCl was added to give a pH of 1.30. The solution was stirred for 1 h, and filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07. After stirring for 2 h and standing overnight the precipitate was filtered, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg, and then at 50° C. and 0.7 mmHg to give title compound (15.5 g 88%) as a pale brown solid. after heating at reflux for 30 min The free acid initially dissolved the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h to evaporate slowly over 40 h to give A sample was removed Ammonia was bubbled through the reaction mixture for 2 h The reaction was then cooled to −16° C. ice (200 g) was added to destroy excess potassium amide all solvents evaporated at 76° C. 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which filtered through Celite to give a clear solution The precipitate was collected by filtration washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C. 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder to give a pH of 1.30 filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07 After stirring for 2 h standing overnight the precipitate was filtered washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C.

Conditions: temp:87.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 L flask was equipped with magnetic stirring bar, cooling bath (liquid nitrogen), stopcock connected to an ammonia cylinder and a vacuum system. The flask was charged with FeCl3 (0.1 g) and evacuated. Ammonium gas was condensed to give liquid ammonium (600 ml). Potassium (19.50 g 0.50 mole) was added in small pieces (each about 0.5 g) under an argon atmosphere. The solution initially became blue but became a grey suspension after heating at reflux for 30 min. Into the potassium amide/liquid ammonia suspension was added in small portions isoquinoline-7-carboxylic acid {ref F. T. Tyson, JACS, 1939,61,183} (17.0 g 0.10 mole). The free acid initially dissolved but the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h. After careful addition of tetraethylethylene diamine (TEEDA) (86 g 0.50 mole), toluene (170 ml) and 18-crown-6 (1 g) the ammonia was allowed to evaporate slowly over 40 h to give a new suspension of the isoquinoline-7-carboxylic acid potassium salt. The reaction mixture was heated to 87° C. for 48 h. A sample was removed and analysed by nmr which indicated that there was still some unreacted starting material present. Ammonia was bubbled through the reaction mixture for 2 h and nmr analysis then revealed that no starting material remained. The reaction was then cooled to −16° C., ice (200 g) was added to destroy excess potassium amide and all solvents evaporated at 76° C. and 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which was dissolved in water (1.2 L) and filtered through Celite to give a clear solution. This was acidified to pH 7 by addition of acetic acid (34 g) and allowed to stand overnight. The precipitate was collected by filtration, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder. The crude product (17.6 g) was dissolved in water (4 L), and concentrated HCl was added to give a pH of 1.30. The solution was stirred for 1 h, and filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07. After stirring for 2 h and standing overnight the precipitate was filtered, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg, and then at 50° C. and 0.7 mmHg to give title compound (15.5 g 88%) as a pale brown solid. after heating at reflux for 30 min The free acid initially dissolved the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h to evaporate slowly over 40 h to give A sample was removed Ammonia was bubbled through the reaction mixture for 2 h The reaction was then cooled to −16° C. ice (200 g) was added to destroy excess potassium amide all solvents evaporated at 76° C. 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which filtered through Celite to give a clear solution The precipitate was collected by filtration washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C. 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder to give a pH of 1.30 filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07 After stirring for 2 h standing overnight the precipitate was filtered washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C.

Conditions: temp:87.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1L flask was equipped with magnetic stirring bar, cooling bath (liquid nitrogen), stopcock connected to an ammonia cylinder and a vacuum system. The flask was charged with FeCl3 (0.1 g) and evacuated. Ammonium gas was condensed to give liquid ammonium (600 ml). Potassium (19.50 g 0.50 mole) was added in small pieces (each about 0.5 g) under an argon atmosphere. The solution initially became blue but became a grey suspension after heating at reflux for 30 min. Into the potassium amide/liquid ammonia suspension was added in small portions isoquinoline-7-carboxylic acid {ref F. T. Tyson, JACS, 1939,61,183} (17.0 g 0.10 mole). The free acid initially dissolved but the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h. After careful addition of tetraethylethylene diamine (TEEDA) (86 g 0.50 mole), toluene (170 ml) and 18-crown-6 (1 g) the ammonia was allowed to evaporate slowly over 40 h to give a new suspension of the isoquinoline-7-carboxylic acid potassium salt. The reaction mixture was heated to 87° C. for 48 h. A sample was removed and analysed by nmr which indicated that there was still some unreacted starting material present. Ammonia was bubbled through the reaction mixture for 2 h and nmr analysis then revealed that no starting material remained. The reaction was then cooled to −16° C., ice (200 g) was added to destroy excess potassium amide and all solvents evaporated at 76° C. and 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which was dissolved in water (1.2L) and filtered through Celite to give a clear solution. This was acidified to pH 7 by addition of acetic acid (34 g) and allowed to stand overnight. The precipitate was collected by filtration, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder. The crude product (17.6 g) was dissolved in water (4L), and concentrated HCl was added to give a pH of 1.30. The solution was stirred for 1 h, and filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07. After stirring for 2 h and standing overnight the precipitate was filtered, washed with water (50 ml×2) and dried by azeotroping with ethanol (50 ml×2) at 50° C. and 7 mmHg, and then at 50° C. and 0.7 mmHg to give title compound (15.5 g 88%) as a pale brown solid. after heating at reflux for 30 min The free acid initially dissolved the formed potassium salt soon precipitated as fine particles to give a suspension which was heated at reflux for 6 h to evaporate slowly over 40 h to give A sample was removed Ammonia was bubbled through the reaction mixture for 2 h The reaction was then cooled to −16° C. ice (200 g) was added to destroy excess potassium amide all solvents evaporated at 76° C. 7 mmHg and then at 65° C. and 0.7 mmHg to give a powder which filtered through Celite to give a clear solution The precipitate was collected by filtration washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C. 7 mmHg then at 50° C. and 0.7 mmHg to give the crude product (17.6 g 94%) as an off-white powder to give a pH of 1.30 filtered through Celite to give a clear solution to which was added concentration ammonia solution to give a pH of 5.07 After stirring for 2 h standing overnight the precipitate was filtered washed with water (50 ml×2) dried by azeotroping with ethanol (50 ml×2) at 50° C.

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

Procedure: The ability of trichlorosilane to redistribute in the presence of tetraethylethylenediamine (TEEDA) and methylene chloride to form a complex comprising dichlorosilane and TEEDA was evaluated. All reactions were performed in a glass flask under a blanket of dry nitrogen. Trichlorosilane was distilled before use. TEEDA was dried by refluxing over CaH2 and then distilled. Dichloromethane was distilled from P2O5 just prior to use. The volumes of materials placed in the flask are provided in Table 1. Materials were added to the flask through a rubber septum by means of a syringe.

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

Procedure: To a mixture of tetrahydrofuran (45 ml) and tetraethylethylenediamine (1.5 ml) were successively added a 1.0M sodium hexamethyldisilazide--tetrahydrofuran solution (0.892 ml) and methyl acetate (71.2 μl) at -78° C. The mixture was stirred for 30 minutes, and then a tetrahydrofuran solution of (2S,4R)-N-tert-butoxycarbonyl-4-(tert-butyldimethylsiloxy)prolinal (196 mg) was added thereto. This solution was stirred for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction solution. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1) to obtain the title compound [209 mg, yield: 87.1%; (R)-isomer (polar compound):(S)-isomer (less polar compound)=1.82:1]. at -78° C This solution was stirred for 30 minutes The mixture was extracted with ethyl acetate The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent was removed in vacuo The residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1)