cyclopropanecarbonitrile

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

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

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:

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

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid KHMDS (6.82 g, 34.3 mmol) is dissolved in THF (60.0 mL) and cooled to −40° C. Cyclopropanecarbonitrile (2.30 g, 34.3 mmol) is added, and the resulting solution is stirred for 30 minutes. A solution of 4-fluorobenzonitrile (4.15 g, 34.3 mmol) in THF (20.0 mL) is added, and the mixture is stirred for 20 minutes at −40° C. followed by 2 hours at room temperature. A saturated solution of NaHCO3 (50.0 mL) is added, and the aqueous phase is extracted with EtOAc (4×40.0 mL). The combined organic phases are dried over MgSO4, filtered and concentrated on the rotovaporator. The product is purified by flash chromatography (CombiFlash), eluting with mixtures of heptanes and EtOAc (0% EtOAc to 70% EtOAc) (743 mg, 4.42 mmol, 13%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.60-1.67 (m, 2H) 1.84-1.90 (m, 2H) 7.49 (d, J=8.59 Hz, 2H) 7.85 (d, J=8.79 Hz, 2H). the mixture is stirred for 20 minutes at −40° C. followed by 2 hours at room temperature the aqueous phase is extracted with EtOAc (4×40.0 mL) The combined organic phases are dried over MgSO4 filtered concentrated on the rotovaporator The product is purified by flash chromatography (CombiFlash)

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

Procedure: Sodium bis(trimethylsilyl)amide (2 M in tetrahydrofuran (THF), 37.5 mL, 75.0 mmol) was slowly added to a solution of cyclopropanecarbonitrile (3.35 g, 49.9 mmol) in THF (30 mL) at room temperature. The reaction mixture was stirred for 20 minutes and then a solution 1-chloromethyl-4-methoxy-benzene (7.83 g, 50.0 mmol) in THF was added. The mixture was heated to reflux for 3 hours and then quenched with a saturated aqueous solution of ammonium chloride (50 mL). The separated aqueous layer was extracted three times with ethyl acetate (50 mL). The combined organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and evaporated to dryness to give crude 1-(4-methoxy-benzyl)-cyclopropanecarbonitrile, which was used directly in the next step. The mixture was heated to reflux for 3 hours quenched with a saturated aqueous solution of ammonium chloride (50 mL) The separated aqueous layer was extracted three times with ethyl acetate (50 mL) The combined organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride, dried over sodium sulfate filtered evaporated to dryness

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

Procedure: A steady stream of HCl gas was slowly passed through a solution of cyclopropancarbonitril (25 g, 373 mmol) in EtOH (17.2 ml). After 15 h the reaction mixture was cooled to 0° C. and diethylether was added dropwise. The precipitated title compound was filtered and obtained as a colourless crystalline material (32.9 g, 220 mmol, 59%). MS: m/e=112.2 (M−H). The precipitated title compound was filtered

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

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture under nitrogen of 26.3 g (260 mmoles) of diisopropylamine and 300 ml of tetrahydrofuran cooled to -75° C., there is added dropwise 125 ml (200 mmoles) of n-butyllithium in a 1.6M hexane solution, then 13.4 g (200 mmoles) of commercial cyclopropanecarbonitrile and finally 25.3 g (200 mmoles) of benzyl chloride. The reaction mixture is stirred 2 hours at -70° C. then 2 days at 20° C. 4 ml of water is added, before washing the reaction mixture with water saturated with NaCl. The organic phase dried over Na2SO4 is concentrated to give a brown liquid, which is purified by distillation. There is obtained 16.8 g (yield=53.5%) of a colorless liquid. b.p.13 =140°-8° C. A new distillation gives a colorless liquid. b.p.0.3 =64°-8° C. 2 days at 20° C before washing the reaction mixture with water saturated with NaCl The organic phase dried over Na2SO4 is concentrated to give a brown liquid, which is purified by distillation

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture under nitrogen of 26.3 g (260 mmoles) of diisopropylamine and 300 ml of tetrahydrofuran cooled to -75° C., there is added dropwise 125 ml (200 mmoles) of n-butyllithium in a 1.6M hexane solution, then 13.4 g (200 mmoles) of commercial cyclopropanecarbonitrile and finally 25.3 g (200 mmoles) of benzyl chloride. The reaction mixture is stirred 2 hours at -70° C. then 2 days at 20° C. 4 ml of water is added, before washing the reaction mixture with water saturated with NaCl. The organic phase dried over Na2SO4 is concentrated to give a brown liquid, which is purified by distillation. There is obtained 16.8 g (yield=53.5%) of a colorless liquid. b.p.13 =140°-8° C. A new distillation gives a colorless liquid. b.p.0.3 =64°-8° C. 2 days at 20° C before washing the reaction mixture with water saturated with NaCl The organic phase dried over Na2SO4 is concentrated to give a brown liquid, which is purified by distillation

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

Procedure: To a stirred solution of 7-methoxybenzofuran (3.0 g) in tetrahydrofuran (60 ml) cooled to -78° C. under an atmosphere of nitrogen was added dropwise n-butyllithium (1.6M in hexanes, 15.2 ml). After stirring at -78° C. for 30 minutes, magnesium bromide diethyl etherate (6.3 g) was added in single portion and the reaction mixture allowed to warm to 0° C. and stirred for 30 minutes. Cyclopropyl cyanide (1.8 ml) was then added dropwise and the mixture allowed to warm slowly to room temperature and stirred for 18 h. Aqueous hydrochloric acid (2M, 50 ml) was added to the reaction mixture and stirring continued for 1 h. The mixture was extracted with ethyl acetate (250 ml), then washed successively with water (50 ml) and brine (50 ml). The organic layer was separated and dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with 5-20% ethyl acetate in hexane afforded the title compound as a yellow oil (0.96 g). to warm to 0° C. stirred for 30 minutes to warm slowly to room temperature stirred for 18 h stirring continued for 1 h The mixture was extracted with ethyl acetate (250 ml) washed successively with water (50 ml) and brine (50 ml) The organic layer was separated dried over magnesium sulfate filtered concentrated in vacuo Purification by flash chromatography on silica eluting with 5-20% ethyl acetate in hexane