N,N-dimethylpropan-2-amine

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

Procedure: A suspension of 3-bromo-4,5-dimethoxybenzaldehyde (1500 g, 6.12 moles, 1.1 eq) and malononitrile (404 g, 6.12 moles, 1.1 eq) in ethanol 99% (12 L, 7 volumes) was stirred at room temperature under N2(g). Dimethylisopropylamine (339 mL, 2.78 moles, 0.5 eq) was added slowly (which caused an exotherm from about 14° C. to about 26° C.) and the reaction mixture was stirred at room temperature for about 2 h under N2(g). The yellow thick suspension was analyzed by HPLC to monitor the appearance of the Knoevenagel intermediate and the disappearance of the aldehyde. 2,3-Diaminophenol (690.66 g, 5.56 moles, 1 eq) was added and the reaction mixture was stirred at room temperature overnight. The resulting beige-brown suspension was filtered and the cake was washed with cold CH2Cl2 (3000 mL). The solids were dried under vacuum to give 2,7,8-triamino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromene (1.9 kg, 82% yield). 1H NMR (300 MHz) (DMSO-d6, ppm): 3.71 (s, 3H), 3.82 (s, 3H), 4.43 (s, 2H), 4.56 (s, 1H), 4.70 (s, 2H), 6.09 (d, J=8 Hz, 1H), 6.26 (d, J=8 Hz, 1H), 6.76 (s, 2H), 6.78 (d, J=2 Hz, 1H), 6.90 (d, J=2 Hz, 1H). from about 14° C. to about 26° C. was stirred at room temperature for about 2 h under N2(g) the reaction mixture was stirred at room temperature overnight The resulting beige-brown suspension was filtered the cake was washed with cold CH2Cl2 (3000 mL) The solids were dried under vacuum

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

Procedure: A suspension of 3-bromo-4,5-dimethoxybenzaldehyde (1500 g, 6.12 moles, 1.1 eq) and malononitrile (404 g, 6.12 moles, 1.1 eq) in ethanol 99% (12 L, 7 volumes) was stirred at room temperature under N2(g). Dimethylisopropylamine (339 mL, 2.78 moles, 0.5 eq) was added slowly (which caused an exotherm from about 14° C. to about 26° C.) and the reaction mixture was stirred at room temperature for about 2 h under N2(g). The yellow thick suspension was analyzed by HPLC to monitor the appearance of the Knoevenagel intermediate and the disappearance of the aldehyde. 2,3-Diaminophenol (690.66 g, 5.56 moles, 1 eq) was added and the reaction mixture was stirred at room temperature overnight. The resulting beige-brown suspension was filtered and the cake was washed with cold CH2Cl2 (3000 mL). The solids were dried under vacuum to give 2,7,8-triamino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromene (1.9 kg, 82% yield). 1H NMR (300 MHz) (DMSO-d6, ppm): 3.71 (s, 3H), 3.82 (s, 3H), 4.43 (s, 2H), 4.56 (s, 1H), 4.70 (s, 2H), 6.09 (d, J=8 Hz, 1H), 6.26 (d, J=8 Hz, 1H), 6.76 (s, 2H), 6.78 (d, J=2 Hz, 1H), 6.90 (d, J=2 Hz, 1H). from about 14° C. to about 26° C. was stirred at room temperature for about 2 h under N2(g) the reaction mixture was stirred at room temperature overnight The resulting beige-brown suspension was filtered the cake was washed with cold CH2Cl2 (3000 mL) The solids were dried under vacuum

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

Procedure: 6 g of N,N-dimethylisopropylamine and 300 ml of heptane were placed under argon in a 500 ml three-necked flask fitted with internal thermometer and gas inlet stopcock. HCl gas from a gas generation apparatus was passed into this reaction mixture for 1 hour. The N,N-dimethylbenzylammonium hydrochloride formed was separated off via a G4 frit, washed with 100 ml of heptane and dried in an oil pump vacuum. 7.4 g (87%) of the desired product were isolated. fitted with internal thermometer and gas inlet stopcock

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

Procedure: 6 g of N,N-dimethylisopropylamine and 300 ml of heptane were placed under argon in a 500 ml three-necked flask fitted with internal thermometer and gas inlet stopcock. HCl gas from a gas generation apparatus was passed into this reaction mixture for 1 hour. The N,N-dimethylbenzylammonium hydrochloride formed was separated off via a G4 frit, washed with 100 ml of heptane and dried in an oil pump vacuum. 7.4 g (87%) of the desired product were isolated. fitted with internal thermometer and gas inlet stopcock

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml jacketed reactor with stirrer, baffles and condenser was initially charged under a nitrogen atmosphere with 103 g of ethylbenzene, 6.3 g of dimethylisopropylamine hydrochloride (0.050 mol, 99%) and 15.5 g of potassium chloride (0.208 mmol). Subsequently, 31.5 g of trifluoromethanesulfinic acid (0.223 mol, 95.0%), 17.9 g of dimethylisopropylamine (0.203 mol, 99%) and 24.2 g of thionyl chloride (203 mmol, 99.7%) were metered in at 0° C. with cooling. After subsequently adding 54.8 g of 5-amino-3-cyano-1-(2,6-dichlor-4-trifluoromethylphenyl)pyrazole, the reaction mixture was stirred at 0° C. for 1 h, then heated to 35° C. over 45 min and stirred at 35° C. for a further 10 h. After the reaction had been quenched with sodium hydroxide solution and extracted with ethyl acetate and ethylbenzene, a nonisolated yield of fipronil of 80% was obtained in the crude solution (determination by means of quantitative HPLC). were metered in at 0° C. with cooling heated to 35° C. over 45 min stirred at 35° C. for a further 10 h After the reaction had been quenched with sodium hydroxide solution extracted with ethyl acetate and ethylbenzene