N,N-dimethylnitrous amide

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

Procedure: nitrosating an aqueous solution of dimethylamine by reaction with dinitrogen tetraoxide and potassium carbonate at a pressure from atomospheric to 50 psig and a temperature from -10° C. to 40° C. to produce an aqueous solution of N-nitrosodimethylamine and potassium nitrate and gaseous carbon dioxide; and,

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

Procedure: nitrosating an aqueous solution of dimethylamine by reaction with dinitrogen tetraoxide and potassium carbonate at a pressure from atomospheric to 50 psig and a temperature from -10° C. to 40° C. to produce an aqueous solution of N-nitrosodimethylamine and potassium nitrate and gaseous carbon dioxide; and,

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

Procedure: nitrosating an aqueous solution of dimethylamine by reaction with dinitrogen tetraoxide and potassium carbonate at a pressure from atomospheric to 50 psig and a temperature from -10° C. to 40° C. to produce an aqueous solution of N-nitrosodimethylamine and potassium nitrate and gaseous carbon dioxide; and,

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6.6 ml diisopropylamine in 150 dry tetrahydrofuran at 0° C. under nitrogen was slowly added 18.4 ml (2.5 m) n-butyllithium. The mixture was cooled to -78° C., and 3.2 ml N-nitrosodimethylamine was then slowly added. The latter mixture was stirred for 30 min, and 6.0 g 5-[5-(2,6-dimethyl-4-cyanophenoxy)pentyl]-3-methylisoxazole in 33 ml dry tetrahydrofuran was added dropwise. The reaction mixture was stirred at -73° C. for 8.5 hours, and 3 ml glacial acetic acid in 10 ml tetrahydrofuran was then added. The reaction mixture was stirred overnight, then concentrated, and the residue dissolved in ethyl acetate. The solution was washed with water and saturated sodium chloride, dried over magnesium sulfate and concentrated to an oily residue. The latter was chromatographed on silica gel and eluted with ethyl acetate/hexane 60:40. The product was recrystallized from ethyl acetate/hexane to give 2.69 g 4-[3,5-dimethyl-4-{[5-(3-methyl-5-isoxazolyl)pentyl]oxy}phenyl]-1-methyl-1H-1,2,3-triazole, m.p. 117-118° C. at 0° C. The reaction mixture was stirred at -73° C. for 8.5 hours The reaction mixture was stirred overnight concentrated the residue dissolved in ethyl acetate The solution was washed with water and saturated sodium chloride dried over magnesium sulfate concentrated to an oily residue The latter was chromatographed on silica gel eluted with ethyl acetate/hexane 60:40 The product was recrystallized from ethyl acetate/hexane

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

Procedure: To a pre cooled (−78° C., internal temp. −70° C.) solution of diisopropyl amine (193.13 g, 1899.04 mmol) in THF (1500 ml) under nitrogen atmosphere was added n-Butyllithium (759.617 ml, 1899.04 mmol, 2.5 M solution in hexane) and stirred for 90 min. Then N,N-dimethyl nitrous amide 2 (134.57 g, 1816.48 mmol) in THF (500 ml) was cannulated portion wise during a period of 30 min. and stirred for 1 h. Then a solution of 2-Fluorobenzonitrile 1 (100.0 g, 825.671 mmol) in THF (500 ml) was cannulated portion wise during a period of 30 min and stirred at −78° C. (internal temp. −70° C.) for 1 h. Then cooling bath was removed and stirred at room temperature for 2 h. The reaction was monitored by TLC and UPLC. The above reaction mass was slowly quenched with saturated solution of ammonium chloride (2000 ml) at room temperature and the aqueous layer was extracted with dichloromethane (5×2000 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated to afford crude mass (170.0 g, 116.21% mass balance). It was purified by gravity column using 30% ethyl acetate in pet ether as an eluent to furnish desired product 4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazole (64.52 g, 44.10% mass balance) as reddish gum. Then it was triturated with methyl tert-butyl ether (1000 ml) and hexane (500 ml), the supernant layer was decanted and the solid was dried to furnish desired product 4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazole (32.9 g, 22.49%) as yellowish solid. of 30 min. stirred for 1 h of 30 min stirred at −78° C. (internal temp. −70° C.) for 1 h Then cooling bath was removed stirred at room temperature for 2 h The above reaction mass was slowly quenched with saturated solution of ammonium chloride (2000 ml) at room temperature the aqueous layer was extracted with dichloromethane (5×2000 ml) The combined organic layer was dried over sodium sulphate filtered concentrated to afford crude mass (170.0 g, 116.21% mass balance) It was purified by gravity column

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

Procedure: nitrosating an aqueous solution of dimethylamine by reaction with dinitrogen tetraoxide and potassium carbonate at a pressure from atomospheric to 50 psig and a temperature from -10° C. to 40° C. to produce an aqueous solution of N-nitrosodimethylamine and potassium nitrate and gaseous carbon dioxide; and,