N-methyl-N-(propan-2-ylideneamino)methanamine

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

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley et al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70° , under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydro- furan was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl)-2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which The tetrahydro- furan was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley et al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70° , under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydro- furan was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl)-2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which The tetrahydro- furan was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: To a solution of acetone N,N-dimethylhydrazone (6.5 mmol) in tetrahydrofuran (THF; 15 ml) under nitrogen is added lithium diisopropylamide (LDA; 7.2 mmol) in THF (15 ml) at 0° for 5 hours. The resulting solution is cooled to -78°, and to it is added 2-[4-(4-trifluoromethylphenoxy)phenoxy]propanal (7.2 mmol). After 1 hour at -78°, the reaction mixture is allowed to warm to 0° and is poured into water/methylene chloride (3:1). The organic phase is separated (3X), and the combined organic extracts are dried over sodium sulfate and concentrated to give 4-hydroxy-5-[4-(4-trifluoromethylphenoxy)-phenoxy]-2-hexanone N,N-dimethylhydrazone (cpd. 1, Table A). The resulting solution is cooled to -78° to warm to 0° The organic phase is separated (3X) the combined organic extracts are dried over sodium sulfate concentrated

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

Procedure: To a solution of acetone N,N-dimethylhydrazone (0.48 g, 4.8 mmol) in 5 ml of THF is added N-butyllithium (4.8 mmol) at -65°, and the mixture is stirred for about 30 minutes. 2-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]propanal (1.50 g, 4.8 mmol) in 5 ml of THF is added dropwise. After several hours at -65°, the reaction mixture is allowed to warm to 0° and is poured onto ice made slightly acidic with 10% acetic acid. The organic phase is separated, washed with water and with NaCl and dried. Solvent is removed to give 4-hydroxy-5-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]-2-hexanone N,N-dimethylhydrazone. After several hours at -65° to warm to 0° is poured onto ice The organic phase is separated washed with water and with NaCl dried Solvent is removed

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

Procedure: To a solution of acetone N,N-dimethylhydrazone (0.32 g, 3.23 mmol) in tetrahydrofuran (THF; 5 ml) is added N-butyllithium (0.21 g, 3.23 mmol) at -65°, and the mixture is stirred for 30 minutes. To this is added dropwise 2-[4-(4-trifluoromethylphenoxy)phenoxy]propanal (1.0 g, 3.23 mmol) in 5 ml of THF, keeping the temperature at or below -60°. After 3 hours at -65°, the reaction mixture is allowed to warm to 0°, and is poured onto 20 g ice made slightly acidic with 10% acetic acid. It is extracted into ether, and the organic extract is washed with water and with NaCl and is dried over sodium sulfate. Solvent is removed, and the residue is purified by prep. TLC (silica gel, 20% ethyl acetate/hexane) to give 4-hydroxy-5-[4-(4-trifluoromethylphenoxy)phenoxy]-2-hexanone (C'; Q1 is CH, Y is hydrogen, Z is trifluoromethyl, R 1 is methyl and R2 is methyl). ##STR21## below -60° After 3 hours at -65° to warm to 0° It is extracted into ether the organic extract is washed with water and with NaCl is dried over sodium sulfate Solvent is removed the residue is purified by prep

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley at al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70°, under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether:hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo-9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydrofuran was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl) 2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether:hexane 1:9 gave a yellow oil which The tetrahydrofuran was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley et al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70° , under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydro- furan was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl)-2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which The tetrahydro- furan was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo