1-butylpyrrolidine

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC

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

Procedure: Methyl bis(pentafluoroethyl)phosphinate, (C2F5)2P(O)OCH3, (3.67 g; 11.6 mmol) is slowly added dropwise to dry and cooled (0° C.) N-butyl-pyrrolidine (1.38 g; 11.2 mmol) (exothermic) in a 25 ml glass flask. A pale-yellow solid forms. The reaction mixture is warmed to room temperature, diluted with 10 ml of n-hexane and stirred for 16.5 h. The readily volatile constituents are removed in vacuo (10−3 mbar) at room temperature. N-Butyl-N-methylpyrrolidinium bis(pentafluoroethyl)phosphinate, [BMPL][(C2F5)2P(O)O], (4.71 g; 10.7 mmol) is isolated as pale-yellow solid in a yield of 96% and a purity of 99%. to dry The readily volatile constituents are removed in vacuo (10−3 mbar) at room temperature

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

Procedure: 11.7 kg of butane-1,4-diol were reacted with 7.3 kg of n-butylamine similarly to Example 1. N-(n-butyl)-pyrrolidine was obtained in 96% yield.

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 250 mg (0.51 mmol) of 4-bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide, and 85 μL (1.02 mmol) of R-(+)-3-pyrrolidinol in 5.0 ml dimethylformamide was stirred at room temperature for 4 hr and at 60° C. for 1 hr. After the mixture was cooled, saturated sodium bicarbonate solution was added and the solution was subsequently extracted with ethyl acetate. The extracts were evaporated to an oil, and purified by preparative TLC. Yield 84.2 mg (33%) yellow solid: mp 215-220° C. After the mixture was cooled the solution was subsequently extracted with ethyl acetate The extracts were evaporated to an oil purified by preparative TLC