ethyl 2-cyano-2-cyclopentylideneacetate

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

Procedure: To an ambient solution of hexamethyldisilazane (17.7 mL, 84.0 mmol) m acetic acid (56 mL) was added sequentially cyclopentanone (5.0 mL, 56.3 mmol) and ethyl 2-cyanoacetate (12.0 mL, 113 mmol). The solution was heated to 70° C. for 15 hours. The reaction was cooled to room temperature and diluted with water (100 mL) and ethyl acetate (100 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×100 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 gel, eluting with 100% hexane to 5% ethyl acetate in hexane, to give the title product as a white, solid. MS (ESI) m/z 180 [M+H]+. The reaction was cooled to room temperature The layers were separated the aqueous was extracted with additional ethyl acetate (2×100 mL) The combined organics were dried with anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was purified by chromatography on SiO2 gel eluting with 100% hexane to 5% ethyl acetate in hexane

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

Procedure: A solution of 39.9 g cyclopentylidene cyanoacetic acid ethyl ester in 350 ml tetrahydrofuran is added dropwise to a solution of 2-methoxybenzyl magnesium chloride (produced from 5.3 g magnesium and 31.2 g 2-methoxybenzyl chloride in 400 ml ether). The mixture is stirred for 2 hours at room temperature. The mixture is treated with a 300 ml 15% ammonium chloride solution. The product is extracted with ether and the ethereal solution concentrated to yield crude α-cyano-[1-(2-methoxybenzyl)cyclopentane]-acetic acid ethyl ester which distilled at 140°-180°/0.002 mm Hg. The product is extracted with ether the ethereal solution concentrated

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

Procedure: The sub-title compound was prepared in a 69% yield analogously to the method described in Organic Synthesis, 39, 25 (1959) from cyclopentanone and ethyl cyanoacetate.

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

Procedure: To an ambient solution of hexamethyldisilazane (17.7 mL, 84.0 mmol) in acetic acid (56 mL) was added sequentially cyclopentanone (5.0 mL, 56.3 mmol) and ethyl 2-cyanoacetate (12.0 mL, 113 mmol). The solution was heated to 70° C. for 15 hours. The reaction was cooled to room temperature and diluted with water (100 mL) and ethyl acetate (100 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×100 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 gel, eluting with 100% hexane to 5% ethyl acetate in hexane, to give the title product as a white, solid. MS (ESI) m/z 180 [M+H]+. The reaction was cooled to room temperature The layers were separated the aqueous was extracted with additional ethyl acetate (2×100 mL) The combined organics were dried with anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was purified by chromatography on SiO2 gel eluting with 100% hexane to 5% ethyl acetate in hexane

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

Procedure: To an ambient solution of hexamethyldisilazane (17.7 mL, 84.0 mmol) m acetic acid (56 mL) was added sequentially cyclopentanone (5.0 mL, 56.3 mmol) and ethyl 2-cyanoacetate (12.0 mL, 113 mmol). The solution was heated to 70° C. for 15 hours. The reaction was cooled to room temperature and diluted with water (100 mL) and ethyl acetate (100 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×100 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 gel, eluting with 100% hexane to 5% ethyl acetate in hexane, to give the title product as a white, solid. MS (ESI) m/z 180 [M+H]+. The reaction was cooled to room temperature The layers were separated the aqueous was extracted with additional ethyl acetate (2×100 mL) The combined organics were dried with anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was purified by chromatography on SiO2 gel eluting with 100% hexane to 5% ethyl acetate in hexane

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

Procedure: A solution of 39.9 g cyclopentylidene cyanoacetic acid ethyl ester in 350 ml tetrahydrofuran is added dropwise to a solution of 2-methoxybenzyl magnesium chloride (produced from 5.3 g magnesium and 31.2 g 2-methoxybenzyl chloride in 400 ml ether). The mixture is stirred for 2 hours at room temperature. The mixture is treated with a 300 ml 15% ammonium chloride solution. The product is extracted with ether and the ethereal solution concentrated to yield crude α-cyano-[1-(2-methoxybenzyl)cyclopentane]-acetic acid ethyl ester which distilled at 140°-180°/0.002 mm Hg. The product is extracted with ether the ethereal solution concentrated