cyclopentanecarbonitrile

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

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

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

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

Procedure: Obtained by operating as in example 87a, from 7.8g (77 mmoles) of diisopropylamine, 48.2 ml of a 1.6M solution of n-butyllithium in hexane, 6.7 g (70 mmoles) of commercial cyclopentanecarbonitrile, 18 ml of 1,3-dimethylimidazolidin-2-one and 20.5 g (71.4 mmoles) of the compound prepared in example 93c, in 110 ml of dry tetrahydrofuran. After distillation, there is obtained 9.6 g (yield=60.0%) of a viscous liquid. b.p.0.4 =160° C. Obtained After distillation

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

Procedure: Obtained by operating as in example 87a, from 7.8g (77 mmoles) of diisopropylamine, 48.2 ml of a 1.6M solution of n-butyllithium in hexane, 6.7 g (70 mmoles) of commercial cyclopentanecarbonitrile, 18 ml of 1,3-dimethylimidazolidin-2-one and 20.5 g (71.4 mmoles) of the compound prepared in example 93c, in 110 ml of dry tetrahydrofuran. After distillation, there is obtained 9.6 g (yield=60.0%) of a viscous liquid. b.p.0.4 =160° C. Obtained After distillation

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

Procedure: Obtained by operating as in example 87a, from 7.8 g (77 mmoles) of diisopropylamine, 48.2 ml of a 1.6M solution of n-butyllithium in hexane, 6.7 g (70 mmoles) of commercial cyclopentanecarbonitrile, 18 ml of 1,3-dimethylimidazolidin-2-one and 20.5 g (71.4 mmoles) of the compound prepared in example 92c in 20 ml of tetrahydrofuran. After distillation, there is obtained 8.8 g (yield=55.0%) of a beige viscous liquid. b.p.0.4 =165 ° C. Obtained After distillation

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

Procedure: To a mixture of 38.9 ml (278 mmoles) of diisopropylamine and 320 ml of tetrahydrofuran, cooled to -60° C., there is successively poured dropwise 174 ml of a solution of 1.6M of n-butyllithium in hexane to which 50 ml of tetrahydrofuran have been added, a mixture of 24 g (252 mmoles) of cyclopentanecarbonitrile and of 50 ml of tetrahydrofuran, 65 ml of 1,3-dimethylimidazolidinone and finally 73.95 g (257 mmoles) of the compound prepared in example 26a. The temperature is allowed to rise to 20° C. After 16 hours at 20° C. the mixture is refluxed during 13 hours. After cooling 1000 ml water are added and the mixture is stirred one hour at room temperature before adding 35 ml concentrated HCl and stirring again one hour. The mixture is extracted with ethyl acetate and is thereafter washed with water, dried over Na2SO4, before being concentrated under reduced pressure. The purification is carried out by distillation which gives 41.1 g (yield=71.1%) of yellow oil. b.P.0.3 =175°-85° C. have been added to rise to 20° C After 16 hours at 20° C. the mixture is refluxed during 13 hours are added stirring again one hour The mixture is extracted with ethyl acetate is thereafter washed with water dried over Na2SO4 before being concentrated under reduced pressure The purification is carried out by distillation which

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

Procedure: To a mixture of 38.9 ml (278 mmoles) of diisopropylamine and 320 ml of tetrahydrofuran, cooled to -60° C., there is successively poured dropwise 174 ml of a solution of 1.6M of n-butyllithium in hexane to which 50 ml of tetrahydrofuran have been added, a mixture of 24 g (252 mmoles) of cyclopentanecarbonitrile and of 50 ml of tetrahydrofuran, 65 ml of 1,3-dimethylimidazolidinone and finally 73.95 g (257 mmoles) of the compound prepared in example 26a. The temperature is allowed to rise to 20° C. After 16 hours at 20° C. the mixture is refluxed during 13 hours. After cooling 1000 ml water are added and the mixture is stirred one hour at room temperature before adding 35 ml concentrated HCl and stirring again one hour. The mixture is extracted with ethyl acetate and is thereafter washed with water, dried over Na2SO4, before being concentrated under reduced pressure. The purification is carried out by distillation which gives 41.1 g (yield=71.1%) of yellow oil. b.P.0.3 =175°-85° C. have been added to rise to 20° C After 16 hours at 20° C. the mixture is refluxed during 13 hours are added stirring again one hour The mixture is extracted with ethyl acetate is thereafter washed with water dried over Na2SO4 before being concentrated under reduced pressure The purification is carried out by distillation which

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

Procedure: In a flask, cyclopentanecarbonitrile (3.53 g, 37.1 mmol) was dissolved in THF (40 mL) and cooled at −78° C. LiHMDS (1.0 M in THF, 41 mL, 41 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (S)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 1.82 g, 12.4 mmol) in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (50-100% EtOAc/heptane) to afford 1.96 g (65%) of (S)-2-methyl-propane-2-sulfinic acid [(R)-1-(1-cyano-cyclopentyl)-ethyl]-amide as a white solid. The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (50-100% EtOAc/heptane)

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

Procedure: In a flask, cyclopentanecarbonitrile (3.53 g, 37.1 mmol) was dissolved in THF (40 mL) and cooled at −78° C. LiHMDS (1.0 M in THF, 41 mL, 41 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (S)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 1.82 g, 12.4 mmol) in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (50-100% EtOAc/heptane) to afford 1.96 g (65%) of (S)-2-methyl-propane-2-sulfinic acid [(R)-1-(1-cyano-cyclopentyl)-ethyl]-amide as a white solid. The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (50-100% EtOAc/heptane)

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

Procedure: Under a nitrogen atmosphere, to a solution of diisopropylamine (0.36 mL) in THF (7.0 mL) was added a 1.6 M solution of n-butyllithium in hexane (1.6 mL) at 0° C., and the mixture was stirred for 10 min. Cyclopentanecarbonitrile (0.28 mL) was added at −78° C., and the mixture was stirred for 30 min. A solution of (4-bromo-3-(bromomethyl)phenoxy) (tert-butyl)dimethylsilane (503 mg) in THF (3.0 mL) was added, and the mixture was stirred at −78° C. for 4 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (471 mg) as a colorless oil. the mixture was stirred for 30 min the mixture was stirred at −78° C. for 4 hr the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: Under a nitrogen atmosphere, to a solution of diisopropylamine (0.36 mL) in THF (7.0 mL) was added a 1.6 M solution of n-butyllithium in hexane (1.6 mL) at 0° C., and the mixture was stirred for 10 min. Cyclopentanecarbonitrile (0.28 mL) was added at −78° C., and the mixture was stirred for 30 min. A solution of (4-bromo-3-(bromomethyl)phenoxy) (tert-butyl)dimethylsilane (503 mg) in THF (3.0 mL) was added, and the mixture was stirred at −78° C. for 4 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (471 mg) as a colorless oil. the mixture was stirred for 30 min the mixture was stirred at −78° C. for 4 hr the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/hexane)