methyl 4-nitrobutanoate

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 solution of 2,5-difluorobenzaldehyde (2.29 mL, 21.1 mmol) in ethanol (42 mL) was added methyl 4-nitrobutyrate (2.51 mL, 21.1 mmol) and the mixture stirred for 5 min. To the reaction mixture was added 2-pyridin-2-ylethanamine (2.61 mL, 21.1 mmol) and the mixture stirred for 10 min. To the mixture was added sodium acetate (1.73 g, 21.1 mmol) followed by glacial acetic acid (2.42 mL, 42.2 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S™) eluting with ethyl acetate/hexane (gradient from 0% to 100%) to give the racemic trans title compound as a yellow gum. LC/MS 362.2 (M+1). the mixture stirred for 10 min the mixture heated at reflux temperature for 48 h The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) the aqueous phase extracted with ethyl acetate (4×25 mL) The combined organic phases were washed with saturated aqueous brine (1×25 mL) dried with anhydrous sodium sulfate filtered the solvent removed in vacuo The yellow oil was purified by column chromatography (silica gel Biotage 40S™) eluting with ethyl acetate/hexane (gradient from 0% to 100%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (2.29 mL, 21.1 mmol) in ethanol (42 mL) was added methyl 4-nitrobutyrate (2.51 mL, 21.1 mmol) and the mixture stirred for 5 min. To the reaction mixture was added 2-pyridin-2-ylethanamine (2.61 mL, 21.1 mmol) and the mixture stirred for 10 min. To the mixture was added sodium acetate (1.73 g, 21.1 mmol) followed by glacial acetic acid (2.42 mL, 42.2 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S™) eluting with ethyl acetate/hexane (gradient from 0% to 100%) to give the racemic trans title compound as a yellow gum. LC/MS 362.2 (M+1). the mixture stirred for 10 min the mixture heated at reflux temperature for 48 h The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) the aqueous phase extracted with ethyl acetate (4×25 mL) The combined organic phases were washed with saturated aqueous brine (1×25 mL) dried with anhydrous sodium sulfate filtered the solvent removed in vacuo The yellow oil was purified by column chromatography (silica gel Biotage 40S™) eluting with ethyl acetate/hexane (gradient from 0% to 100%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (0.765 mL, 7.04 mmol) in ethanol (15 mL) was added methyl 4-nitrobutyrate (0.901 mL, 7.04 mmol) and the mixture stirred for 5 minutes. To the reaction mixture was added 2-(2-fluorophenyl)ethylamine (0.87 mL, 7.04 mmol) and the mixture stirred for 10 minutes. To the mixture was added sodium acetate (0.577 g, 7.04 mmol) followed by glacial acetic acid (0.806 mL, 14.07 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S) eluting with ethyl acetate/hexane (gradient from 0% to 60%) to give the racemic trans title compound as a yellow gum. LC/MS 379.2 (M+1). the mixture stirred for 10 minutes the mixture heated at reflux temperature for 48 h The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) the aqueous phase extracted with ethyl acetate (4×25 mL) The combined organic phases were washed with saturated aqueous brine (1×25 mL) dried with anhydrous sodium sulfate filtered the solvent removed in vacuo The yellow oil was purified by column chromatography (silica gel Biotage 40S) eluting with ethyl acetate/hexane (gradient from 0% to 60%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (0.765 mL, 7.04 mmol) in ethanol (15 mL) was added methyl 4-nitrobutyrate (0.901 mL, 7.04 mmol) and the mixture stirred for 5 minutes. To the reaction mixture was added 2-(2-fluorophenyl)ethylamine (0.87 mL, 7.04 mmol) and the mixture stirred for 10 minutes. To the mixture was added sodium acetate (0.577 g, 7.04 mmol) followed by glacial acetic acid (0.806 mL, 14.07 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S) eluting with ethyl acetate/hexane (gradient from 0% to 60%) to give the racemic trans title compound as a yellow gum. LC/MS 379.2 (M+1). the mixture stirred for 10 minutes the mixture heated at reflux temperature for 48 h The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) the aqueous phase extracted with ethyl acetate (4×25 mL) The combined organic phases were washed with saturated aqueous brine (1×25 mL) dried with anhydrous sodium sulfate filtered the solvent removed in vacuo The yellow oil was purified by column chromatography (silica gel Biotage 40S) eluting with ethyl acetate/hexane (gradient from 0% to 60%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (1.09 g, 7.67 mmol) in ethanol (20 mL) were added methyl 4-nitrobutyrate (1.13 g, 7.04 mmol), benzylamine (0.98 mL, 7.67 mmol), sodium acetate (1.26 g, 15.3 mmol) and acetic acid (0.88 mL, 15.4 mmol). The mixture was stirred at rt for 12 h and then heated at reflux temperature overnight. After evaporation, the residue was purified by column chromatography (silica gel Biotage 40M™) eluting with ethyl acetate/hexane (gradient from 3% to 50%) to give the title compound as the racemic trans isomer. LC-MS: 347.1 (M+1). heated at reflux temperature overnight After evaporation the residue was purified by column chromatography (silica gel Biotage 40M™) eluting with ethyl acetate/hexane (gradient from 3% to 50%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (1.09 g, 7.67 mmol) in ethanol (20 mL) were added methyl 4-nitrobutyrate (1.13 g, 7.04 mmol), benzylamine (0.98 mL, 7.67 mmol), sodium acetate (1.26 g, 15.3 mmol) and acetic acid (0.88 mL, 15.4 mmol). The mixture was stirred at rt for 12 h and then heated at reflux temperature overnight. After evaporation, the residue was purified by column chromatography (silica gel Biotage 40M™) eluting with ethyl acetate/hexane (gradient from 3% to 50%) to give the title compound as the racemic trans isomer. LC-MS: 347.1 (M+1). heated at reflux temperature overnight After evaporation the residue was purified by column chromatography (silica gel Biotage 40M™) eluting with ethyl acetate/hexane (gradient from 3% to 50%)

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

Procedure: To a solution of 2,5-difluorobenzaldehyde (0.765 mL, 7.04 mmol) in ethanol (15 mL) were added methyl 4-nitrobutyrate (0.901 mL, 7.04 mmol) and methylamine (7.04 mL, 14.07 mmol). The mixture was heated at reflux temperature overnight. After evaporation, the residue was purified by column chromatography (silica gel Biotage 40M) eluting with ethyl acetate/hexane (gradient from 40% to 60%) to give the title compound as the racemic trans isomer. LC-MS: 271.05 (M+1). The mixture was heated at reflux temperature overnight After evaporation the residue was purified by column chromatography (silica gel Biotage 40M) eluting with ethyl acetate/hexane (gradient from 40% to 60%)