ethyl 2-(benzylideneamino)acetate

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: Diisopropylamine (2.34 ml, 16.7 mmoles) is added to anhydrous THF (75 ml) and cooled to -10° C. At this point 2.24M n-BuLi (6.8 ml, 15.2 mmoles) is added slowly. After complete addition the reaction mixture is stirred for 10 minutes before being cooled to -78° C. At that temperature ethyl N-benzylideneglycinate (4) (2.9 g, 15.2 mmoles) is added and stirring is allowed to proceed for 15 minutes before aldehyde (8) (4.0 g, 15.2 mmoles), dissolved in anhydrous THF (25 ml), is added dropwise to the yellow anion. After complete addition the reaction is stirred another 11/2 hours before being poured into cold 5% aqueous NH4Cl. This mixture is extracted with CHCl3 (3×100 ml). The combined extracts are washed with saturated aqueous NaCl, dried over MgSO4, filtered and evaporated to dryness. The oily residue is taken up in THF (300 ml) and shaken with 5% aqueous HCl (200 ml) in a separatory funnel. This mixture is washed with Et2O (3×100 ml), basified with solid NaHCO3 and extracted with CHCl3 (3×150 ml). The combined extracts are washed with saturated aqueous NaCl (1×150 ml), dried over MgSO4, filtered and evaporated to dryness in vacuo to yield 4.0 g (72% yield) of the desired compound as a yellow glass. 'H-N.M.R. (CHCl3 /TMS): δ=1.20 (t, 3H, --CH2CH3); 1.28 (t, 3H, --CH2CH3 ); 1.45-2.20 (m, 4H, --CH2CH2 --); 2.46 (broad s, 2H, --NH2); 3.18-4.00 (m, 2H, >CH--NH2, CHOH); 4.19 (q, 2H, --CH2CH3); 4.25 (q, 2H, --CH2CH3); 4.53-5.08 (m, 1H, >CH--NH--); 7.05-7.97 ppm (m, 5H, Ph). After complete addition the reaction mixture before being cooled to -78° C stirring is added dropwise to the yellow anion After complete addition the reaction is stirred another 11/2 hours This mixture is extracted with CHCl3 (3×100 ml) The combined extracts are washed with saturated aqueous NaCl dried over MgSO4 filtered evaporated to dryness shaken with 5% aqueous HCl (200 ml) in a separatory funnel This mixture is washed with Et2O (3×100 ml) extracted with CHCl3 (3×150 ml) The combined extracts are washed with saturated aqueous NaCl (1×150 ml) dried over MgSO4 filtered evaporated to dryness in vacuo

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

Procedure: Diisopropylamine (2.34 ml, 16.7 mmoles) is added to anhydrous THF (75 ml) and cooled to -10° C. At this point 2.24M n-BuLi (6.8 ml, 15.2 mmoles) is added slowly. After complete addition the reaction mixture is stirred for 10 minutes before being cooled to -78° C. At that temperature ethyl N-benzylideneglycinate (4) (2.9 g, 15.2 mmoles) is added and stirring is allowed to proceed for 15 minutes before aldehyde (8) (4.0 g, 15.2 mmoles), dissolved in anhydrous THF (25 ml), is added dropwise to the yellow anion. After complete addition the reaction is stirred another 11/2 hours before being poured into cold 5% aqueous NH4Cl. This mixture is extracted with CHCl3 (3×100 ml). The combined extracts are washed with saturated aqueous NaCl, dried over MgSO4, filtered and evaporated to dryness. The oily residue is taken up in THF (300 ml) and shaken with 5% aqueous HCl (200 ml) in a separatory funnel. This mixture is washed with Et2O (3×100 ml), basified with solid NaHCO3 and extracted with CHCl3 (3×150 ml). The combined extracts are washed with saturated aqueous NaCl (1×150 ml), dried over MgSO4, filtered and evaporated to dryness in vacuo to yield 4.0 g (72% yield) of the desired compound as a yellow glass. 'H-N.M.R. (CHCl3 /TMS): δ=1.20 (t, 3H, --CH2CH3); 1.28 (t, 3H, --CH2CH3 ); 1.45-2.20 (m, 4H, --CH2CH2 --); 2.46 (broad s, 2H, --NH2); 3.18-4.00 (m, 2H, >CH--NH2, CHOH); 4.19 (q, 2H, --CH2CH3); 4.25 (q, 2H, --CH2CH3); 4.53-5.08 (m, 1H, >CH--NH--); 7.05-7.97 ppm (m, 5H, Ph). After complete addition the reaction mixture before being cooled to -78° C stirring is added dropwise to the yellow anion After complete addition the reaction is stirred another 11/2 hours This mixture is extracted with CHCl3 (3×100 ml) The combined extracts are washed with saturated aqueous NaCl dried over MgSO4 filtered evaporated to dryness shaken with 5% aqueous HCl (200 ml) in a separatory funnel This mixture is washed with Et2O (3×100 ml) extracted with CHCl3 (3×150 ml) The combined extracts are washed with saturated aqueous NaCl (1×150 ml) dried over MgSO4 filtered evaporated to dryness in vacuo

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: 260 g (2.3 moles) of potassium tert.-butylate are added a little at a time to 200 g (1.05 moles) of N-benzylideneglycine ethyl ester and 90.5 ml (1.05 moles) of 1,2-dibromoethane in 900 ml of dry diethyl ether and 300 l of dry dimethylsulfoxide, so that the well-stirred mixture remains at from 25° to 35° C. The mixture is stirred at room temperature overnight and excess base is then neutralized by addition of 4N hydrochloric acid. The mixture is diluted with 1.5 l of water and the ethereal phase is separated off, washed with twice 300 ml of water, dried with sodium sulfate and evaporated to give 155 g (68%) of ethyl N-benzylidene-1-aminocyclopropanecarboxylate as an oil. remains at from 25° to 35° C the ethereal phase is separated off washed with twice 300 ml of water dried with sodium sulfate evaporated

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

Procedure: 25.2 g (1.05 moles) of sodium hydride are added a little at a time under nitrogen to 100 g (0.523 mole) of N-benzylideneglycine ethyl ester and 45.1 ml (0.523 mole) of 1,2-dibromoethane in 500 ml of dry diethyl ether and 170 ml of dry dimethylsulfoxide, so that the well-stirred mixture remains at from 20° to 30° C. The mixture is stirred at room temperature overnight and filtered, and 1 l of water is added to the filtrate. The ethereal phase is separated off, washed with twice 200 ml of water, dried over sodium sulfate and evaporated under reduced pressure to give 80 g (70%) of ethyl N-benzylidene-1-aminocyclopropanecarboxylate as an oil. remains at from 20° to 30° C filtered 1 l of water is added to the filtrate The ethereal phase is separated off washed with twice 200 ml of water dried over sodium sulfate evaporated under reduced pressure

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

Procedure: To a mixture of 10.6 g of ethyl phenylglycinate hydrochloride 2 (49.3 mmol), 100 mL of dichloromethane, 5 ml of benzaldehyde (49.2 mmol) and 30 g of magnesium sulfate (249.2 mmol) were added at room temperature, under a nitrogen atmosphere, 21.25 mL of triethylamine (152.46 mmol). After stirring for 17 h the heterogeneous reaction mixture was filtered through celite and the solid was washed with 100 mL of dichloromethane. The solvents were evaporated under reduced pressure and the viscous oil thus obtained was stirred with 80 mL of diethyl ether and 80 mL of water until dissolution. After decantation, the organic layer was dried over sodium sulphate and the solvent was evaporated under vacuum. The immine ester 3 (12.4 g, 94% yield) was obtained as a yellow pale oil. were added at room temperature, under a nitrogen atmosphere was filtered through celite the solid was washed with 100 mL of dichloromethane The solvents were evaporated under reduced pressure the viscous oil thus obtained After decantation, the organic layer was dried over sodium sulphate the solvent was evaporated under vacuum

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

Procedure: To ethyl glycinate hydrochloride (36.4 g) suspended in 500 ml methylene chloride were added magnesium sulfate (22 g) and triethylamine (72 ml, 52.4 g). Benzaldehyde (27.6 g) was added dropwise at 15°-20° C. with stirring. The mixture was stirred at room temperature for two hours, filtered and stripped. To the residue was added 300 ml diethylether and 150 ml brine. After separation the organic layer was collected, and the aqueous layer was extracted with 100 ml ether. The organic phases were combined, dried (MgSO4), filtered and stripped to yield the title product as a pale yellow oil. The mixture was stirred at room temperature for two hours filtered To the residue was added 300 ml diethylether and 150 ml brine After separation the organic layer was collected the aqueous layer was extracted with 100 ml ether dried (MgSO4) filtered