BENZYL ETHYL MALONATE

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:

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

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (17.8 g, 445 mmol) was added portionwise to a solution of benzyl ethyl malonate (98.9, 445 mmol) in dry DMF (280 ml) and stirred for 10 minutes. Cooled to 10° C. over 30 minutes. 2,4-difluoro-1-nitrobenzene (48.9 ml, 445 mmol) was added and stirred at room temperature for 16 hours. The reaction mixture was quenched with 2N hydrochloric acid (150 ml) to pH 3-4 then extracted ×2 with ether. The combined organics washed with 2× water and brine, dried over magnesium sulphate and evaporated to a yellow oil. Purified by chromatography on silica gel eluting with 5% ethyl acetate in hexane to give the title compound as a yellow oil (11.66, 32.3 mmol). LC/MS: Rt=3.39, [MH]− 360. stirred at room temperature for 16 hours The reaction mixture was quenched with 2N hydrochloric acid (150 ml) to pH 3-4 then extracted ×2 with ether The combined organics washed with 2× water and brine dried over magnesium sulphate evaporated to a yellow oil Purified by chromatography on silica gel eluting with 5% ethyl acetate in hexane

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

Procedure: Benzyl ethyl malonate (2.9 g, 12.6 mmol) in dry DMF (20 ml) was cooled in an ice bath and the temperature monitored whilst sodium hydride (504 mg, 12.6 mmol) was added portionwise. This was stirred at room temperature for 10 minutes until H2 evolution ceased. 3,4-Difluoronitrobenzene (2 g, 12.6 mmol) was added under an argon atmosphere and gave a dark red colour change. The reaction mixture was heated at 100° C. for 20 hours under argon. Thin layer chromatography (20% ethyl acetate in hexane) showed completion of the reaction. The reaction mixture was cooled to room temperature and partitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml). The aqueous layer was extracted with ethyl acetate (2×75 ml) and the combined organic fractions were evaporated to a yellow oil. Purification by chromatography on silica gel eluting with 0-20% ethyl acetate in hexane gave the title compound as a yellow oil (3.86 g, 10.6 mmol). was added portionwise gave a dark red colour change The reaction mixture was heated at 100° C. for 20 hours under argon completion of the reaction The reaction mixture was cooled to room temperature partitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml) The aqueous layer was extracted with ethyl acetate (2×75 ml) the combined organic fractions were evaporated to a yellow oil Purification by chromatography on silica gel eluting with 0-20% ethyl acetate in hexane

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

Procedure: To a mixture of 5-bromo-2-nitropyridine (8.66 g, 42.7 mmol) and benzyl ethyl malonate (9.50 g, 42.7 mmol) in tetrahydrofuran (160 ml) and dimethylformamide (40 ml) was added K2CO3 (5.90 g, 42.7 mmol) and stirred under reflux temperature for 20 h. The mixture was diluted with water (11) and extracted with ethyl acetate (3×200 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated to give 5.26 g of title compound as orange oil. under reflux temperature for 20 h extracted with ethyl acetate (3×200 ml) The organic layer was washed with brine dried (MgSO4) concentrated

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

Procedure: To a mixture of 5-bromo-2-nitropyridine (8.66 g, 42.7 mmol) and benzyl ethyl malonate (9.50 g, 42.7 mmol) in tetrahydrofuran (160 ml) and dimethylformamide (40 ml) was added K2CO3 (5.90 g, 42.7 mmol) and stirred under reflux temperature for 20 h. The mixture was diluted with water (11) and extracted with ethyl acetate (3×200 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated to give 5.26 g of title compound as orange oil. under reflux temperature for 20 h extracted with ethyl acetate (3×200 ml) The organic layer was washed with brine dried (MgSO4) concentrated

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

Procedure: To a mixture of 5-bromo-2-nitropyridine (8.66 g, 42.7 mmol) and benzyl ethyl malonate (9.50 g, 42.7 mmol) in tetrahydrofuran (160 ml) and dimethylformamide (40 ml) was added K2CO3 (5.90 g, 42.7 mmol) and stirred under reflux temperature for 20 h. The mixture was diluted with water (1 l) and extracted with ethyl acetate (3×200 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated to give 5.26 g of title compound as orange oil. under reflux temperature for 20 h extracted with ethyl acetate (3×200 ml) The organic layer was washed with brine dried (MgSO4) concentrated

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

Procedure: To a mixture of 5-bromo-2-nitropyridine (8.66 g, 42.7 mmol) and benzyl ethyl malonate (9.50 g, 42.7 mmol) in tetrahydrofuran (160 ml) and dimethylformamide (40 ml) was added K2CO3 (5.90 g, 42.7 mmol) and stirred under reflux temperature for 20 h. The mixture was diluted with water (1 ) and extracted with ethyl acetate (3×200 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated to give 5.26 g of title compound as orange oil. under reflux temperature for 20 h extracted with ethyl acetate (3×200 ml) The organic layer was washed with brine dried (MgSO4) concentrated

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

Procedure: To a mixture of 5-bromo-2-nitropyridine (8.66 g, 42.7 mmol) and benzyl ethyl malonate (9.50 g, 42.7 mmol) in tetrahydrofuran (160 ml) and dimethylformamide (40 ml) was added K2CO3 (5.90 g, 42.7 mmol) and stirred under reflux temperature for 20 h. The mixture was diluted with water (11) and extracted with ethyl acetate (3×200 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated to give 5.26 g of title compound as orange oil. under reflux temperature for 20 h extracted with ethyl acetate (3×200 ml) The organic layer was washed with brine dried (MgSO4) concentrated