methyl 4-(4-fluorophenyl)-4-oxobutanoate

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: A solution of 3-(p-fluorobenzoyl)propionic acid (58.8 g.) in anhydrous methanol (250 ml.) was treated with concentrated sulphuric acid (3.2 ml.) and the mixture heated at reflux temperature for 10 hours. It was then concentrated to a volume of 100 ml., cooled and diluted with ice-water. The resultant solid was collected and crystallised from ligroin to yield the ester (59.7 g.), m.p. 48°-50 ° C. the mixture heated at reflux temperature for 10 hours It was then concentrated to a volume of 100 ml , cooled diluted with ice-water The resultant solid was collected crystallised from ligroin

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

Procedure: In a 500 ml round-bottomed flask, 0.095 mol of the compound obtained in Step B is dissolved in 250 ml of methanol. 1 g of 10% activated palladium-on-carbon is added and magnetic stirring is carried out under a hydrogen atmosphere for 12 hours. The palladiated carbon is then filtered off, and the methanol is evaporated off under reduced pressure. The oil obtained is purified by chromatography on silica gel. is added The palladiated carbon is then filtered off the methanol is evaporated off under reduced pressure The oil obtained is purified by chromatography on silica gel

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

Procedure: In a 500 ml round-bottomed flask, 0.095 mol of the compound obtained in Step B is dissolved in 250 ml of methanol. 1 g of 10% activated palladium-on-carbon is added and magnetic stirring is carried out under a hydrogen atmosphere for 12 hours. The palladiated carbon is then filtered off, and the methanol is evaporated off under reduced pressure. The oil obtained is purified by chromatography on silica gel. is added The palladiated carbon is then filtered off the methanol is evaporated off under reduced pressure The oil obtained is purified by chromatography on silica gel

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

Procedure: A solution of 3-(p-fluorobenzoyl)propionic acid (58.8 g.) in anhydrous methanol (250 ml.) was treated with concentrated sulphuric acid (3.2 ml.) and the mixture heated at reflux temperature for 10 hours. It was then concentrated to a volume of 100 ml., cooled and diluted with ice-water. The resultant solid was collected and crystallised from ligroin to yield the ester (59.7 g.), m.p. 48°-50 ° C. the mixture heated at reflux temperature for 10 hours It was then concentrated to a volume of 100 ml , cooled diluted with ice-water The resultant solid was collected crystallised from ligroin

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

Procedure: A solution of 3-(p-fluorobenzoyl)propionic acid (58.8 g.) in anhydrous methanol (250 ml.) was treated with concentrated sulphuric acid (3.2 ml.) and the mixture heated at reflux temperature for 10 hours. It was then concentrated to a volume of 100 ml., cooled and diluted with ice-water. The resultant solid was collected and crystallised from ligroin to yield the ester (59.7 g.), m.p. 48°-50 ° C. the mixture heated at reflux temperature for 10 hours It was then concentrated to a volume of 100 ml , cooled diluted with ice-water The resultant solid was collected crystallised from ligroin

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 BH3.THF (1M, 5.7 mL, 5.7 mmol) in 40 mL anhydrous THF was dropwise added at room temperature (S)-2-methyl-CBS-oxazaborolidine (952 μL, 0.952 mmol, 1M in toluene). After stirring for 5 minutes, methyl 4-(4-fluorophenyl)-4-oxobutanoate (2.0 g, 9.5 mmol) was added as a solution in 25 mL THF. The reaction mixture was stirred for 30 min at room temperature and then quenched by the slow addition of saturated aqueous ammonium chloride (60 mL) The resulting mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers washed with brine (2×40 mL) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the product isolated by silica gel Flash chromatography to afford 1.7 g of the title compound as a colorless oil. The reaction mixture was stirred for 30 min at room temperature quenched by the slow addition of saturated aqueous ammonium chloride (60 mL) The resulting mixture was extracted with ethyl acetate (3×50 mL) the combined organic layers washed with brine (2×40 mL) dried over Na2SO4 The solvent was evaporated under reduced pressure the product isolated by silica gel Flash chromatography

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

Procedure: To a solution of 3-(4-fluorobenzoyl)-propionic acid (1.98 g, 10.0 =ol) in methanol (25 mL) was added 0.5 mL of conc. sulfuric acid. The resulting solution was stirred at room temperature under argon for 2 hours. The reaction mixture was neutralized with saturated sodium bicarbonate, the methanol was removed via rotary evaporator and the residue was dissolved in 50 mL of ethyl acetate. The resulting solution was washed with saturated sodium bicarbonate (3×50 nL) and brine (50 -mL), dried over sodium sulfate and the solvent was removed in vacuo to give Methyl 3-(4-fluorobenzoyl)-propionate (2 g, 94%). IR (film) 3448, 3111, 3076, 3003, 3958, 1734, 1678, 1601, 1423, 1300, 1240, 1155, 1099 cm−1; 1H-NMR (CDCl3) δ 7.97 (2H, dd, J=9.0, 5.5 Hz), 7.10 (2H, t, J=8.9 Hz), 3.67 (3H, s), 3.25 (2H, t, J=6.6 Hz), 2.73 (2H, t, J=6.6 Hz); 13C-NMR (CDCl3) δ 196.50, 173.34, 167.54, 164.17, 132.98, 130.77, 115.91, 115.62, 51.91, 33.31, 28.00. the methanol was removed via rotary evaporator the residue was dissolved in 50 mL of ethyl acetate The resulting solution was washed with saturated sodium bicarbonate (3×50 nL) and brine (50 -mL) dried over sodium sulfate the solvent was removed in vacuo

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

Procedure: To a solution of 3-(4-fluorobenzoyl)-propionic acid (1.98 g, 10.0 mmol) in methanol (25 mL) was added 0.5 mL of conc. sulfuric acid. The resulting solution was stirred at room temperature under argon for 2 hours. The reaction mixture was neutralized with saturated sodium bicarbonate, the methanol was removed via rotary evaporator and the residue was dissolved in 50 mL of ethyl acetate. The resulting solution was washed with saturated sodium bicarbonate (3×50 mL) and brine (50 mL), dried over sodium sulfate and the solvent was removed in vacuo to give Methyl 3-(4-fluorobenzoyl)-propionate (2 g, 94%). IR (film) 3448, 3111, 3076, 3003, 3958, 1734, 1678, 1601, 1423, 1300, 1240, 1155, 1099 cm-1 ; 1H-NMR (CDCl3) δ 7.97 (2H, dd, J=9.0, 5.5 Hz), 7.10 (2H, t, J=8.9 Hz), 3.67 (3H, s) , 3.25 (2H, t, J=6.6 Hz), 2.73 (2H, t, J=6.6 Hz); 13C-NMR (CDCl3) δ 196.50, 173.34, 167.54, 164.17, 132.98, 130.77, 115.91, 115.62, 51.91, 33.31, 28.00. the methanol was removed via rotary evaporator the residue was dissolved in 50 mL of ethyl acetate The resulting solution was washed with saturated sodium bicarbonate (3×50 mL) and brine (50 mL) dried over sodium sulfate the solvent was removed in vacuo