sodium;butan-1-olate

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4.8 g of sodium butylate in 74 g of n-butanol was added to 156 g of n-butyl 3-pentenoate at room temperature, and the mixture was heated to 65° C. and stirred at this temperature for 6 hours. The reaction mixture was cooled, n-butanol was distilled off, the residue was extracted by shaking with 25 ml of water, and the organic phase was dried over Na2SO4. Fractional distillation gave 95 g (41% of theory) of n-butyl 3-n-butoxyvalerate. The reaction mixture was cooled n-butanol was distilled off the residue was extracted by shaking with 25 ml of water the organic phase was dried over Na2SO4 Fractional distillation

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

Procedure: A mixture of [1,3-dioxo-5-(4-propoxy-phenoxy)-1,3-dihydro-isoindol-2-yl]-acetic acid ethyl ester (2.485 g, 6.48 mmol), sodium butoxide, and butanol (14.3 mmol, 27 mL butanol) was heated at 90° C. to 100° C. for 2 h. Then the reaction mixture was allowed to cool to ambient temperature, acidified with 2 M HCl to pH 3-4, and extracted with EtOAc. The organic phase was then washed with water and saturated NaCl solution, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography to give the title compound (722 mg). ESI MS (m/z): 412 (M+H)+. was heated at 90° C. to 100° C. for 2 h extracted with EtOAc The organic phase was then washed with water and saturated NaCl solution dried over anhydrous sodium sulfate concentrated in vacuo The residue was purified by column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Freshly cut sodium metal, 0.40 g, was dissolved in 22 ml of n-butanol at 65° C. under a nitrogen atmosphere. A mixture of 3.0 g of (5-iodo-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid methyl ester in 22 ml of n-butanol was added to the sodium butoxide solution and the reaction mixture was heated to 80° C. for 2 h. The cooled reaction mixture was acidified with 100 ml of 1 M hydrochloric acid to give a solid precipitate. The solid was collected by filtration and separated by silica gel chromatography (eluant; 19:1 dichloromethane:ethyl acetate) to give 0.219 g of 4-hydroxy-7-iodo-1-oxo-1,2-dihydro-isoquinoline-3-carboxylic acid butyl ester: MS-(−)-ion, M−1=386.0 amu, and 0.150 g of 4-hydroxy-6-iodo-1-oxo-1,2-dihydro-isoquinoline-3-carboxylic acid butyl ester: MS-(−) ion, M−1=386.0 amu. The cooled reaction mixture to give a solid precipitate The solid was collected by filtration separated by silica gel chromatography (eluant; 19:1 dichloromethane:ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Freshly cut sodium metal, 0.40 g, was dissolved in 22 ml of n-butanol at 65° C. under a nitrogen atmosphere. A mixture of 3.0 g of (5-iodo-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid methyl ester in 22 ml of n-butanol was added to the sodium butoxide solution and the reaction mixture was heated to 80° C. for 2 h. The cooled reaction mixture was acidified with 100 ml of 1 M hydrochloric acid to give a solid precipitate. The solid was collected by filtration and separated by silica gel chromatography (eluant; 19:1 dichloromethane:ethyl acetate) to give 0.219 g of 4-hydroxy-7-iodo-1-oxo-1,2-dihydro-isoquinoline-3-carboxylic acid butyl ester: MS-(−)-ion, M−1=386.0 amu, and 0.150 g of 4-hydroxy-6-iodo-1-oxo-1,2-dihydro-isoquinoline-3-carboxylic acid butyl ester: MS-(−) ion, M−1=386.0 amu. The cooled reaction mixture to give a solid precipitate The solid was collected by filtration separated by silica gel chromatography (eluant; 19:1 dichloromethane:ethyl acetate)

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

Procedure: 376 g of crude 2-(4-chlorophenoxymethyl)-2-(1,1,2-trimethylpropyl)-oxirane dissolved in 400 ml of n-butanol are added dropwise to a boiling solution of 13.4 g (0.14 mol) of sodium butanolate and 97 g (1.4 mols of 1,2,4-triazole in 400 ml of n-butanol in 1.5 hours. After boiling under reflux for 22 hours, the solvent is removed by distillation under reduced pressure and 500 ml of dichloromethane are added to the residue. Precipitated 2-(4-chlorophenoxymethyl)-1-(1,2,4-triazol-4-yl)-3,3,4-trimethylpentan-2-ol (15 g; melting point 173°-174° C.) is filtered off from the mixture, the filtrate is washed twice with 250 ml of water each time and dried over anhydrous sodium sulphate and the solvent is removed by distillation. The residue is chromatographed on silica gel using trichloromethane as eluant. 174 g of 2-(4-chlorophenoxymethyl)-1-(1,2,4-triazol-1-yl)-3,3,4-trimethylpentan-2-ol are thus obtained in the form of colorless crystals of melting point 59°-60° C. under reflux for 22 hours the solvent is removed by distillation under reduced pressure and 500 ml of dichloromethane are added to the residue Precipitated 2-(4-chlorophenoxymethyl)-1-(1,2,4-triazol-4-yl)-3,3,4-trimethylpentan-2-ol (15 g; melting point 173°-174° C.) is filtered off from the mixture the filtrate is washed twice with 250 ml of water each time dried over anhydrous sodium sulphate the solvent is removed by distillation The residue is chromatographed on silica gel

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

Procedure: To date, only one 8-alkoxymethylergoline has been prepared and isolated. In particular, Zikan and Semonsky prepared D6-methyl-8-n-butoxymethylergoline by reaction of sodium butylate and the corresponding 8-chloromethylergoline. These workers reported that the reaction, when carried out with most sodium alcoholates, led primarily to elimination of hydrochloric acid and provided the corresponding 8-methylenergoline derivative; see Coll. Czech. Chem. Comm. 39, 614 (1974). Indeed, reaction of D-6-methyl-8-chloromethylergoline with sodium methoxide under the conditions taught by Zikan and Semonsky, effected only elimination of the elements of hydrochloric acid, affording exclusively the corresponding 8-methylenergoline. isolated In particular, Zikan and Semonsky prepared D6-methyl-8-n-butoxymethylergoline These workers reported that the reaction, when

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

Procedure: To date, only one 8-alkoxymethylergoline has been prepared and isolated. In particular, Zikan and Semonsky prepared D6-methyl-8-n-butoxymethylergoline by reaction of sodium butylate and the corresponding 8-chloromethylergoline. These workers reported that the reaction, when carried out with most sodium alcoholates, led primarily to elimination of hydrochloric acid and provided the corresponding 8-methylenergoline derivative; see Coll. Czech. Chem. Comm. 39, 614 (1974). Indeed, reaction of D-6-methyl-8-chloromethylergoline with sodium methoxide under the conditions taught by Zikan and Semonsky, effected only elimination of the elements of hydrochloric acid, affording exclusively the corresponding 8-methylenergoline. isolated In particular, Zikan and Semonsky prepared D6-methyl-8-n-butoxymethylergoline These workers reported that the reaction, when

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

Procedure: A 1 l five-neck flask equipped with thermometer, reflux condenser, high-performance stirrer and dropping funnel was charged with 447 g (3 mol) of butyl ethylphosphonite (produced as in Example 3) and 159 g (3 mol) of acrylonitrile. While stirring, 15 ml of sodium butoxide (30% strength in butanol) are added dropwise at a rate such that a reaction temperature of max. 120° C. becomes established. The crude product thus obtained is distilled in vacuo to obtain 554 g (91% of theory) of butyl ethyl(2-cyanoethyl)phosphinate as colorless liquid. A 1 l five-neck flask equipped with thermometer reflux condenser, high-performance stirrer 120° C. The crude product thus obtained is distilled in vacuo

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

Procedure: An oven dried Schlenk tube equipped with a rubber septum was purged with argon. The septum was removed, and the tube was charged with palladium acetate (2.2 mg, 0.01 mmol, 2 mol %) and (+)-2-(dicyclohexylphosphino)-2′-(dimethylamino)-1,1′-binaphthyl (10.9 mg, 0.011 mmol 2.2 mol %). The tube was capped with the septum, purged with argon, and toluene (2 mL) and triethylamine (5 mg, 0.05 mmol) were added through the septum. The mixture was stirred at room temperature for 3 min, then vinyl bromide (1.0 mL 1.0 mmol) was added through septum. The septum was removed and 2-methyl-5-(N-methyl-anilinomethylene)cyclopentanone (108 mg, 0.5 mmol) and sodium 1-butoxide (96 mg, 1.0 mmol) were added. The tube was capped with the septum and purged with argon. Additional toluene (4 mL) was added and the mixture was stirred at room temperature for 2 h. The mixture was quenched with saturated aqueous ammonium chloride (5 mL), diluted with ether (20 mL) and poured into a separatory funnel. The layers were separated and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel to afford 113 mg (94%) of the title compound. The ee was determined to be 85% by chiral HPLC analysis. An oven dried Schlenk tube equipped with a rubber septum was purged with argon The septum was removed The tube was capped with the septum were added through the septum The septum was removed The tube was capped with the septum purged with argon Additional toluene (4 mL) was added the mixture was stirred at room temperature for 2 h The mixture was quenched with saturated aqueous ammonium chloride (5 mL) diluted with ether (20 mL) poured into a separatory funnel The layers were separated the aqueous layer was extracted with ether (20 mL) The combined organic layers were washed with brine (20 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography on silica gel

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

Procedure: An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge. The septum was removed and the tube was charged with tris(dibenzylideneacetone)dipalladium (0) (23 mg, 0.025 mmol, 10 mol % Pd), (S)-BINAP (46 mg, 0.075 mmol, 15 mol %) and 2-pentyl-5-(N-methyl-anilinomethylene)cyclopentanone (136 mg, 0.5 mmol). Toluene (2 mL) was added and the mixture was stirred for 1 min at room temperature. 4-bromobenzotrifluoride (225 mg, 1.0 mmol) and sodium 1-butoxide (96 mg, 1.0 mmol) were added to the tube. The tube was capped with the septum, purged with argon, and additional toluene (4 mL) was added through the septum. The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed as judged by GC analysis. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ether (20 mL). The mixture was poured into a separatory funnel and the layers were separated. The aqueous layer was extracted with ether (20 mL), and the combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel to afford 148 mg (71%) of the title compound. The ee was determined to be 90% by chiral HPLC analysis. An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge The septum was removed The tube was capped with the septum purged with argon, and additional toluene (4 mL) was added through the septum The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed The mixture was cooled to room temperature quenched with saturated aqueous ammonium chloride (10 mL) diluted with ether (20 mL) The mixture was poured into a separatory funnel the layers were separated The aqueous layer was extracted with ether (20 mL) the combined organic layers were washed with brine (20 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography on silica gel

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

Procedure: An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge. The septum was removed and the tube was charged with tris(dibenzylideneacetone)dipalladium (0) (23 mg, 0.025 mmol, 10 mol % Pd), (S)-BINAP (46 mg, 0.075 mmol, 15 mol %) and 2-pentyl-5-(N-methyl-anilinomethylene)-cyclopentanone (136 mg, 0.5 mmol). Toluene (2 mL) was added and the mixture was stirred for 1 min at room temperature. Bromobenzene (157 mg, 1.0 mmol) and sodium 1-butoxide (96 mg, 1.0 mmol) were added to the tube. The tube was capped with the septum, purged with argon, and additional toluene (4 mL) was added through the septum. The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed as judged by GC analysis. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ether (20 mL). The mixture was poured into a separatory: funnel and the layers were separated. The aqueous layer was extracted with ether (20 mL), the combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel to afford 146 mg (84%) of the title compound. The ee was determined to be 93% by chiral HPLC analysis. An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge The septum was removed The tube was capped with the septum purged with argon, and additional toluene (4 mL) was added through the septum The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed The mixture was cooled to room temperature quenched with saturated aqueous ammonium chloride (10 mL) diluted with ether (20 mL) The mixture was poured into a separatory: funnel the layers were separated The aqueous layer was extracted with ether (20 mL) the combined organic layers were washed with brine (20 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography on silica gel

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

Procedure: An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge. The septum was removed and the tube was charged with tris(dibenzylideneacetone)dipalladium (0) (23 mg, 0.025 mmol, 10 mol % Pd), (S)-BINAP (46 mg, 0.075 mmol, 15 mol %) and 2-pentyl-5-(N-methyl-anilinomethylene)-cyclopentanone (136 mg, 0.5 mmol). Toluene (2 mL) was added and the mixture was stirred for 1 min at room temperature. Bromobenzene (157 mg, 1.0 mmol) and sodium 1-butoxide (96 mg, 1.0 mmol) were added to the tube. The tube was capped with the septum, purged with argon, and additional toluene (4 mL) was added through the septum. The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed as judged by GC analysis. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ether (20 mL). The mixture was poured into a separatory: funnel and the layers were separated. The aqueous layer was extracted with ether (20 mL), the combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel to afford 146 mg (84%) of the title compound. The ee was determined to be 93% by chiral HPLC analysis. An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge The septum was removed The tube was capped with the septum purged with argon, and additional toluene (4 mL) was added through the septum The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed The mixture was cooled to room temperature quenched with saturated aqueous ammonium chloride (10 mL) diluted with ether (20 mL) The mixture was poured into a separatory: funnel the layers were separated The aqueous layer was extracted with ether (20 mL) the combined organic layers were washed with brine (20 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography on silica gel