5-chloro-2-(trifluoromethyl)benzonitrile

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

Procedure: 29.2 ml of borane-THF complex (29.2 mmol) are slowly added dropwise under argon to an ice-cooled solution of 5-chloro-2-(trifluoromethyl)benzonitrile (1.50 g, 7.3 mmol) in 45 ml of anhydrous THF. After the end of the addition, the mixture is heated under reflux for 1 hr, then stirred overnight at RT with cooling. 30 ml of 1 N hydrochloric acid are then added dropwise with ice-cooling. The THF is removed on the rotary evaporator. The precipitated solid is filtered off and discarded. The filtrate is diluted with water and extracted twice with dichloromethane. These organic phases are also discarded. The acidic aqueous phase is adjusted to pH 14 with 1 N aqueous sodium hydroxide and extracted three times with dichloromethane. The combined organic phases are dried over sodium sulphate and freed of solvent on the rotary evaporator. The residue is taken up in 20 ml diethyl ether and treated with 3 ml of a 4 N solution of hydrogen chloride in dioxan, during which the product precipitates. The solvent is completely removed on the rotary evaporator, then in high vacuum. 1.89 g (99% of theory) of the title compound are isolated. After the end of the addition the mixture is heated under reflux for 1 hr with cooling cooling The THF is removed on the rotary evaporator The precipitated solid is filtered off The filtrate is diluted with water extracted twice with dichloromethane extracted three times with dichloromethane The combined organic phases are dried over sodium sulphate freed of solvent on the rotary evaporator treated with 3 ml of a 4 N solution of hydrogen chloride in dioxan, during which the product precipitates The solvent is completely removed on the rotary evaporator

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

Procedure: 0.619 g (7.2 mmol) of methyl acrylate, 38.7 mg (120 μmol) of NBu4Br, 6.7 mg (30 μmol) of palladium acetate and 26.7 mg (120 μmol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.23 g (6 mmol) of 3-cyano-4-trifluoromethylchlorobenzene and 1.53 ml (7.2 mmol) of dicylohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130° C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water and the product is extracted by shaking with t-butyl methyl ether. After drying the organic phase over MgSO4, the solvent is removed under reduced pressure and the product is isolated. Yellowish, crystalline solid, yield: 1.31 g (85.5% of theory). The Schlenk vessel is placed in a heating bath at 130° C. the product is extracted by shaking with t-butyl methyl ether After drying the organic phase over MgSO4 the solvent is removed under reduced pressure the product is isolated

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

Procedure: 0.619 g (7.2 mmol) of methyl acrylate, 38.7 mg (120 μmol) of NBu4Br, 6.7 mg (30 μmol) of palladium acetate and 26.7 mg (120 μmol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.23 g (6 mmol) of 3-cyano-4-trifluoromethylchlorobenzene and 1.53 ml (7.2 mmol) of dicylohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130° C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water and the product is extracted by shaking with t-butyl methyl ether. After drying the organic phase over MgSO4, the solvent is removed under reduced pressure and the product is isolated. Yellowish, crystalline solid, yield: 1.31 g (85.5% of theory). The Schlenk vessel is placed in a heating bath at 130° C. the product is extracted by shaking with t-butyl methyl ether After drying the organic phase over MgSO4 the solvent is removed under reduced pressure the product is isolated

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

Procedure: 29.2 ml of borane-THF complex (29.2 mmol) are slowly added dropwise under argon to an ice-cooled solution of 5-chloro-2-(trifluoromethyl)benzonitrile (1.50 g, 7.3 mmol) in 45 ml of anhydrous THF. After the end of the addition, the mixture is heated under reflux for 1 hr, then stirred overnight at RT with cooling. 30 ml of 1 N hydrochloric acid are then added dropwise with ice-cooling. The THF is removed on the rotary evaporator. The precipitated solid is filtered off and discarded. The filtrate is diluted with water and extracted twice with dichloromethane. These organic phases are also discarded. The acidic aqueous phase is adjusted to pH 14 with 1 N aqueous sodium hydroxide and extracted three times with dichloromethane. The combined organic phases are dried over sodium sulphate and freed of solvent on the rotary evaporator. The residue is taken up in 20 ml diethyl ether and treated with 3 ml of a 4 N solution of hydrogen chloride in dioxan, during which the product precipitates. The solvent is completely removed on the rotary evaporator, then in high vacuum. 1.89 g (99% of theory) of the title compound are isolated. After the end of the addition the mixture is heated under reflux for 1 hr with cooling cooling The THF is removed on the rotary evaporator The precipitated solid is filtered off The filtrate is diluted with water extracted twice with dichloromethane extracted three times with dichloromethane The combined organic phases are dried over sodium sulphate freed of solvent on the rotary evaporator treated with 3 ml of a 4 N solution of hydrogen chloride in dioxan, during which the product precipitates The solvent is completely removed on the rotary evaporator