methyl 2-pyrrolidin-2-ylideneacetate

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

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

Procedure: To a flask containing a 60% dispersion of NaH (0.91 g, 22.7 mmol), and toluene (60 mL), under nitrogen, is added Pyrrolidin-2-ylidene-acetic acid methyl ester (3.2 g, 22.7 mmol) and the mixture is refluxed for 1 h. The reaction mixture was cooled to 0° C. and a solution of m-cyanobenzylbromide (4.45 g, 22.7 mmol) in toluene (60 mL) is added dropwise. The reaction is allowed to warm to RT and then heated at 60° C. overnight. The mixture is cooled to RT and with vigorous stirring 1 N HCl is added to obtain a pH of 6. The toluene was decanted and dried over Na2SO4 and concentrated. Purification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc) gave the title compound as a wet solid (3.2 g, 12.5 mmol). 1H NMR (CDCl3, 300 MHz) 8.32(br. s, 1H), 7.48-7.25(m, 4H), 3.63(s, 3H), 3.62-3.55(m, 2H), 3.53(s, 2H), 2.66-2.48(m, 2H), 2.10-1.90(m, 2H). the mixture is refluxed for 1 h to warm to RT heated at 60° C. overnight The mixture is cooled to RT is added to obtain a pH of 6 The toluene was decanted dried over Na2SO4 concentrated Purification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc)

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

Procedure: To a flask containing NaOCH3 (1.21 g, 21.3 mmol) and dry MeOH (50 mL) under nitrogen is added 2,2-dimethyl-5-pyrrolidin-2-ylidene-[1,3]dioxane-4,6-dione (4.5 g, 21.3 mmol) and the contents are refluxed overnight. The reaction is concentrated and the residue is diluted with H20 (50 mL). 1 N HCl is added to obtain a pH of 6 and the mixture is extracted with CHCl3 (3×30 mL). The organic fractions are combined, dried over MgSO4 and concentrated. The crude product is purified by flash chromatography (50% EtOAc/hexanes) to give the title cormpouiid as a white solid (2.57 g, 18.2 mmol). 1H NMR (CDCl3, 300 MHz) 4.49(br. s, 1H), 3.63(s, 3H), 3.62-3.46(m, 2H), 1.75-1.50(m, 2H), 2.11-1.90(m, 2H). the contents are refluxed overnight The reaction is concentrated the residue is diluted with H20 (50 mL) 1 N HCl is added to obtain a pH of 6 the mixture is extracted with CHCl3 (3×30 mL) dried over MgSO4 concentrated The crude product is purified by flash chromatography (50% EtOAc/hexanes)

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

Procedure: To a flask containing NaOCH3 (1.21 g, 21.3 mmol) and dry MeOH (50 mL) under nitrogen is added 2,2-dimethyl-5-pyrrolidin-2-ylidene-[1,3]dioxane-4,6-dione (4.5 g, 21.3 mmol) and the contents are refluxed overnight. The reaction is concentrated and the residue is diluted with H20 (50 mL). 1 N HCl is added to obtain a pH of 6 and the mixture is extracted with CHCl3 (3×30 mL). The organic fractions are combined, dried over MgSO4 and concentrated. The crude product is purified by flash chromatography (50% EtOAc/hexanes) to give the title cormpouiid as a white solid (2.57 g, 18.2 mmol). 1H NMR (CDCl3, 300 MHz) 4.49(br. s, 1H), 3.63(s, 3H), 3.62-3.46(m, 2H), 1.75-1.50(m, 2H), 2.11-1.90(m, 2H). the contents are refluxed overnight The reaction is concentrated the residue is diluted with H20 (50 mL) 1 N HCl is added to obtain a pH of 6 the mixture is extracted with CHCl3 (3×30 mL) dried over MgSO4 concentrated The crude product is purified by flash chromatography (50% EtOAc/hexanes)

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

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

Procedure: To a flask containing a 60% dispersion of NaH (0.91 g, 22.7 mmol), and toluene (60 mL), under nitrogen, is added Pyrrolidin-2-ylidene-acetic acid methyl ester (3.2 g, 22.7 mmol) and the mixture is refluxed for 1 h. The reaction mixture was cooled to 0° C. and a solution of m-cyanobenzylbromide (4.45 g, 22.7 mmol) in toluene (60 mL) is added dropwise. The reaction is allowed to warm to RT and then heated at 60° C. overnight. The mixture is cooled to RT and with vigorous stirring 1 N HCl is added to obtain a pH of 6. The toluene was decanted and dried over Na2SO4 and concentrated. Purification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc) gave the title compound as a wet solid (3.2 g, 12.5 mmol). 1H NMR (CDCl3, 300 MHz) 8.32(br. s, 1H), 7.48-7.25(m, 4H), 3.63(s, 3H), 3.62-3.55(m, 2H), 3.53(s, 2H), 2.66-2.48(m, 2H), 2.10-1.90(m, 2H). the mixture is refluxed for 1 h to warm to RT heated at 60° C. overnight The mixture is cooled to RT is added to obtain a pH of 6 The toluene was decanted dried over Na2SO4 concentrated Purification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc)

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

Procedure: To a flask containing NaOCH3 (1.21 g, 21.3 mmol) and dry MeOH (50 mL) under nitrogen is added 2,2-dimethyl-5-pyrrolidin-2-ylidene-[1,3]dioxane-4,6-dione (4.5 g, 21.3 mmol) and the contents are refluxed overnight. The reaction is concentrated and the residue is diluted with H20 (50 mL). 1 N HCl is added to obtain a pH of 6 and the mixture is extracted with CHCl3 (3×30 mL). The organic fractions are combined, dried over MgSO4 and concentrated. The crude product is purified by flash chromatography (50% EtOAc/hexanes) to give the title cormpouiid as a white solid (2.57 g, 18.2 mmol). 1H NMR (CDCl3, 300 MHz) 4.49(br. s, 1H), 3.63(s, 3H), 3.62-3.46(m, 2H), 1.75-1.50(m, 2H), 2.11-1.90(m, 2H). the contents are refluxed overnight The reaction is concentrated the residue is diluted with H20 (50 mL) 1 N HCl is added to obtain a pH of 6 the mixture is extracted with CHCl3 (3×30 mL) dried over MgSO4 concentrated The crude product is purified by flash chromatography (50% EtOAc/hexanes)