ethyl but-2-enoate

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: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: To a suspension of NaH (9.72 g, 243 mmol, 60% in mineral oil) in toluene (100 mL), ethoxycarbonylamino-acetic acid ethyl ester (38 g, 187 mmol) is added at 0° C. The reaction is left stirring for 5 h at the same temperature. At that point but-2-enoic acid ethyl ester (25.6 g, 224 mmol) is added and the reaction allowed to warm up to rt and stirred for further 2 h. Ethanol (30 mL) is added and the reaction is then evaporated. The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL), then formamidine acetate (343 g, 1189 mmol) is added followed by sodium ethoxide (47.2 g, 694 mmol). The reaction is left stirring at 90° C. for 8 h. The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added followed by DCM (1 L). The water layer is extracted two times with DCM. The organics are dried and evaporate. The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10) to give the title compound. MS (ESI) m/z 252.2 (M+1). is added at 0° C The reaction is left stirred for further 2 h the reaction is then evaporated The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL) The reaction is left stirring at 90° C. for 8 h The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added The water layer is extracted two times with DCM The organics are dried evaporate The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10)

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

Procedure: To a suspension of NaH (9.72 g, 243 mmol, 60% in mineral oil) in toluene (100 mL), ethoxycarbonylamino-acetic acid ethyl ester (38 g, 187 mmol) is added at 0° C. The reaction is left stirring for 5 h at the same temperature. At that point but-2-enoic acid ethyl ester (25.6 g, 224 mmol) is added and the reaction allowed to warm up to rt and stirred for further 2 h. Ethanol (30 mL) is added and the reaction is then evaporated. The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL), then formamidine acetate (343 g, 1189 mmol) is added followed by sodium ethoxide (47.2 g, 694 mmol). The reaction is left stirring at 90° C. for 8 h. The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added followed by DCM (1 L). The water layer is extracted two times with DCM. The organics are dried and evaporate. The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10) to give the title compound. MS (ESI) m/z 252.2 (M+1). is added at 0° C The reaction is left stirred for further 2 h the reaction is then evaporated The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL) The reaction is left stirring at 90° C. for 8 h The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added The water layer is extracted two times with DCM The organics are dried evaporate The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10)

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

Procedure: To a freshly prepared solution of MeONa (432 g, 7.99 mol) in MeOH (2 L) is added 3-oxo-butyric acid ethyl ester (1.04 kg, 7.99 mol) over 15 min and the mixture is stirred on an ice bath for an additional 15 min. But-2-enoic acid ethyl ester (912 g, 7.99 mol) is added dropwise at RT and the mixture stirred at RT for 1 h and then the reaction mixture is refluxed for 2 h. After cooling to RT, the precipitated solids are filtered off, dissolved in cold water (1.5 L), acidified with HCl (3 M) to pH to 7 and the resulting mixture is extracted with EtOAc (4×800 mL). The combined organic phase is dried over anhydrous Na2SO4, the solvents are evaporated in vacuo and the residue recrystallized from hexane to give 2-hydroxy-6-methyl-4-oxo-cyclohex-1-enecarboxylic acid methyl ester (672 g, 42% yield). the mixture stirred at RT for 1 h the reaction mixture is refluxed for 2 h the precipitated solids are filtered off dissolved in cold water (1.5 L) the resulting mixture is extracted with EtOAc (4×800 mL) The combined organic phase is dried over anhydrous Na2SO4 the solvents are evaporated in vacuo the residue recrystallized from hexane

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

Procedure: To a freshly prepared solution of MeONa (432 g, 7.99 mol) in MeOH (2 L) is added 3-oxo-butyric acid ethyl ester (1.04 kg, 7.99 mol) over 15 min and the mixture is stirred on an ice bath for an additional 15 min. But-2-enoic acid ethyl ester (912 g, 7.99 mol) is added dropwise at RT and the mixture stirred at RT for 1 h and then the reaction mixture is refluxed for 2 h. After cooling to RT, the precipitated solids are filtered off, dissolved in cold water (1.5 L), acidified with HCl (3 M) to pH to 7 and the resulting mixture is extracted with EtOAc (4×800 mL). The combined organic phase is dried over anhydrous Na2SO4, the solvents are evaporated in vacuo and the residue recrystallized from hexane to give 2-hydroxy-6-methyl-4-oxo-cyclohex-1-enecarboxylic acid methyl ester (672 g, 42% yield). the mixture stirred at RT for 1 h the reaction mixture is refluxed for 2 h the precipitated solids are filtered off dissolved in cold water (1.5 L) the resulting mixture is extracted with EtOAc (4×800 mL) The combined organic phase is dried over anhydrous Na2SO4 the solvents are evaporated in vacuo the residue recrystallized from hexane