ethyl 2-bromo-3-phenylpropanoate

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: EThyl 2-bromo-3-phenylpropionate (1.95 g) was treated with 3.05 g N-methylpiperazine as described in Example 95 to afford 0.30 g pure product after chromatography (9:1 CH2Cl2 :MeOH). NMR (300 MHz, CDCl3) delta 1.10 (d, J=7 Hz, 3H), 2.26 (s, 3H), 3.37 (m, 1H), 4.00 (m, 2H).

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

Procedure: A solution of 2.0 g ethyl 2-bromo-3-phenylpropionate and 2.8 g morpholine in 5 mL DMF was stirred overnight at RT. The mixture was diluted with 75 mL 1% HCl and washed 3×50 mL ether. The aqueous phase was made basic and extracted 3×100 mL EtOAc. The combined extracts were dried over MgSO4, filtered and concentrated. The residue was chromatographed (35% EtOAc:Hex) to afford 0.8 g pure product. NMR (300 MHz, CDCl3) delta 1.12 (t, J=7 Hz, 3H), 3.36 (m, 1H), 4.04 (m, 2H). washed 3×50 mL ether extracted 3×100 mL EtOAc The combined extracts were dried over MgSO4 filtered concentrated The residue was chromatographed (35% EtOAc:Hex)

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

Procedure: A solution of 2.0 g ethyl 2-bromo-3-phenylpropionate and 2.8 g morpholine in 5 mL DMF was stirred overnight at RT. The mixture was diluted with 75 mL 1% HCl and washed 3×50 mL ether. The aqueous phase was made basic and extracted 3×100 mL EtOAc. The combined extracts were dried over MgSO4, filtered and concentrated. The residue was chromatographed (35% EtOAc:Hex) to afford 0.8 g pure product. NMR (300 MHz, CDCl3) delta 1.12 (t, J=7 Hz, 3H), 3.36 (m, 1H), 4.04 (m, 2H). washed 3×50 mL ether extracted 3×100 mL EtOAc The combined extracts were dried over MgSO4 filtered concentrated The residue was chromatographed (35% EtOAc:Hex)

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

Procedure: 630 mg (6.7 mmol) of 2-aminopyridine and 1.72 g (6.7 mmol) of ethyl 2-bromo-3-phenylpropionate were refluxed under heating in 50 ml of ether for 12 hours. The reaction mixture was allowed to cool to room temperature and ether was removed by decantation. The residue was added with and dissolved in 30 ml of absolute ethanol, which was added to a solution of 150 mg (6.5 mmol) of sodium in 10 ml of absolute ethanol and stirred at room temperature for one hour. Then, 0.8 ml (6.5 mmol) of 4-fluorobenzylbromide was added and stirred for overnight. The reaction mixture was added to ice water and extracted with methylene chloride. Then, the solvent was removed under reduced pressure and the residue was purified with silica gel column chromatography, thus obtaining 22 mg (yield: 1%) of the titled compound. ether was removed by decantation The residue was added with and dissolved in 30 ml of absolute ethanol stirred for overnight extracted with methylene chloride Then, the solvent was removed under reduced pressure the residue was purified with silica gel column chromatography

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

Procedure: 630 mg (6.7 mmol) of 2-aminopyridine and 1.72 g (6.7 mmol) of ethyl 2-bromo-3-phenylpropionate were refluxed under heating in 50 ml of ether for 12 hours. The reaction mixture was allowed to cool to room temperature and ether was removed by decantation. The residue was added with and dissolved in 30 ml of absolute ethanol, which was added to a solution of 150 mg (6.5 mmol) of sodium in 10 ml of absolute ethanol and stirred at room temperature for one hour. Then, 0.8 ml (6.5 mmol) of 4-fluorobenzylbromide was added and stirred for overnight. The reaction mixture was added to ice water and extracted with methylene chloride. Then, the solvent was removed under reduced pressure and the residue was purified with silica gel column chromatography, thus obtaining 22 mg (yield: 1%) of the titled compound. ether was removed by decantation The residue was added with and dissolved in 30 ml of absolute ethanol stirred for overnight extracted with methylene chloride Then, the solvent was removed under reduced pressure the residue was purified with silica gel column chromatography

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

Procedure: Ethylenediamine (25 g.) is added to a stirred solution of ethyl 2-bromo-3-phenylpropionate (XXVII, Example 61, 14.0 g.) in THF (100 ml.) and ethanol (300 ml.). After 20 hours at 20°-25° the solvents are removed under reduced pressure and the residual oil is partitioned between ethyl acetate-1N sodium hydroxide solution. The ethyl acetate extract is washed with water, saline, and concentrated. The residual oil is applied to a silica gel column which is eluted with chloroform-methanol (9/1). Fractions containing the product are pooled, concentrated to a residue and recrystallized from ethyl acetate-SSB to give 3-(phenylmethyl)piperazinone, m.p. 92°-93°. After 20 hours at 20°-25° the solvents are removed under reduced pressure the residual oil is partitioned between ethyl acetate-1N sodium hydroxide solution The ethyl acetate extract is washed with water, saline concentrated is eluted with chloroform-methanol (9/1) Fractions containing the product concentrated to a residue recrystallized from ethyl acetate-SSB

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

Procedure: Ethyl bromo-(phenylmethyl)propandioate (XXVI, Example 60, 130 g.) is heated under reduced pressure to 140° with vigorous evolution of carbon dioxide. When decarboxylation is complete (about 5 minutes), the mixture is distilled to give ethyl 2-bromo-3-phenylpropionate, b.p. 120°/30 mm. (about 5 minutes) the mixture is distilled

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

Procedure: Ethyl bromo-(phenylmethyl)propandioate (XXVI, Example 60, 130 g.) is heated under reduced pressure to 140° with vigorous evolution of carbon dioxide. When decarboxylation is complete (about 5 minutes), the mixture is distilled to give ethyl 2-bromo-3-phenylpropionate, b.p. 120°/30 mm. (about 5 minutes) the mixture is distilled

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 544 mg (3.13 mmol) of 4-bromopyridin-2(1H)-one and 845 mg (3.3 mmol) of ethyl 2-bromo-3-phenylpropanoate (racemate) in the presence of 1.15 eq. of sodium hydride and 2.3 eq. of lithium bromide were reacted according to General Method 4C (stirred at 65° C. for 1.5 h). Yield: 572 mg (51% of theory)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 544 mg (3.13 mmol) of 4-bromopyridin-2(1H)-one and 845 mg (3.3 mmol) of ethyl 2-bromo-3-phenylpropanoate (racemate) in the presence of 1.15 eq. of sodium hydride and 2.3 eq. of lithium bromide were reacted according to General Method 4C (stirred at 65° C. for 1.5 h). Yield: 572 mg (51% of theory)