布洛芬杂质21

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Propionyl chloride (13.0 ml) was added to a suspension of aluminum chloride (20.0 g) in dichloromethane (200 ml) at 0° C. After the mixture was stirred at 0° C. for 1 hour, isobutylbenzene (23.6 ml) was added to the mixture. The mixture was stirred at 0° C. for 2 hours and poured into ice water. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residual oil was distilled under reduced pressure to give 4'-isobutylpropiophenone as a colourless oil (24.4 g). The mixture was stirred at 0° C. for 2 hours The organic layer was washed with water dried over magnesium sulfate evaporated The residual oil was distilled under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Propionyl chloride (13.0 ml) was added to a suspension of aluminum chloride (20.0 g) in dichloromethane (200 ml) at 0° C. After the mixture was stirred at 0° C. for 1 hour, isobutylbenzene (23.6 ml) was added to the mixture. The mixture was stirred at 0° C. for 2 hours and poured into ice water. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residual oil was distilled under reduced pressure to give 4'-isobutylpropiophenone as a colourless oil (24.4 g). The mixture was stirred at 0° C. for 2 hours The organic layer was washed with water dried over magnesium sulfate evaporated The residual oil was distilled under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Propionyl chloride (13.0 ml) was added to a suspension of aluminum chloride (20.0 g) in dichloromethane (200 ml) at 0° C. After the mixture was stirred at 0° C for 1 hour, isobutylbenzene (23.6 ml) was added to the mixture. The mixture was stirred at 0° C. for 2 hours and poured into ice water. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residual oil was distilled under reduced pressure to give 4'-isobutylpropiophenone as a colourless oil (24.4 g). The mixture was stirred at 0° C. for 2 hours The organic layer was washed with water dried over magnesium sulfate evaporated The residual oil was distilled under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Propionyl chloride (13.0 ml) was added to a suspension of aluminum chloride (20.0 g) in dichloromethane (200 ml) at 0° C. After the mixture was stirred at 0° C for 1 hour, isobutylbenzene (23.6 ml) was added to the mixture. The mixture was stirred at 0° C. for 2 hours and poured into ice water. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residual oil was distilled under reduced pressure to give 4'-isobutylpropiophenone as a colourless oil (24.4 g). The mixture was stirred at 0° C. for 2 hours The organic layer was washed with water dried over magnesium sulfate evaporated The residual oil was distilled under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5.40 g of 4'-isobutylpropiophenone in 15 ml of ethyl acetate, 3.00 g of pyrrolidine hydrochloride, 1.30 g of paraformaldehyde and 0.5 ml of 22% hydrogen chloride-ethyl acetate were treated in the same manner as that described for Example 3 to give 3.53 g of hydrochloride of the desired compound which were recrystallized from methyl ethyl ketone as colorless scales, mp 127°-128°.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 5.11 g. portion of the crude ibuprofen methyl ester prepared as described above was dissolved in 20 ml. of hexane and 12 ml. of methanol and cooled to 0° to 5° C. Then 6.0 g. (75 mmole) of a 50% sodium hydroxide solution was added and the resulting mixture was heated under reflux for 2 hours. On cooling, the mixture was transferred to a separatory funnel with about 50 ml. of 1 N sodium hydroxide solution and hexane. The hexane layer was extracted with about 10 ml. of 1 N aqueous sodium hydroxide and the combined aqueous layer was extracted with 50 ml. of fresh hexane. The neutral fraction isolated from the combined hexane extracts consisted primarily of p-isobutylpropiophenone. The aqueous layer was acidified with 50% aqueous sulfuric acid and extracted 3 times with 50 ml. portions of hexane. The combined hexane extracts were washed 3 times with 50 ml. portions of water and dried over sodium sulfate. Removal of solvent by vacuum evaporation gave crude ibuprofen as a pale yellow solid, weighing 4.20 g., having a purity of 96.7% by Glc analysis, again the impurities being about 1.4% p-isobutylbenzoic acid and 1.1% of the meta isomer of ibuprofen. The crude yield was 80.8% of theory. Recrystallization of the crude ibuprofen from hexane (2 ml./g.) gave 3.44 g. (70.3% chemical yield) ibuprofen. above was dissolved in 20 ml the resulting mixture was heated under reflux for 2 hours On cooling the mixture was transferred to a separatory funnel with about 50 ml The hexane layer was extracted with about 10 ml of 1 N aqueous sodium hydroxide and the combined aqueous layer was extracted with 50 ml The neutral fraction isolated from the combined hexane extracted 3 times with 50 ml The combined hexane extracts were washed 3 times with 50 ml portions of water and dried over sodium sulfate Removal of solvent by vacuum evaporation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 11.33 g. (0.10 mole) of methyl acetimidate hydrochloride, prepared by known procedures, in a 100 ml. 3-necked, round-bottomed flask there was added a solution of 9.71 g. (actual 9.42 g.; 49.6 mmole) of crude p-isobutylpropiophenone, prepared as described in Part A above, in 23 ml. of absolute methanol. The resulting solution was stirred for 12 hours at room temperature to insure complete reaction. Gas liquid chromatographic analysis (Glc analysis) of an aliquot of the reaction mixture indicated greater than 99% ketal formation. The resulting mixture was filtered to remove the precipitated ammonium chloride and concentrated under vacuum. Hexane (50 ml.) was added to the residue and the resulting solution was again filtered to remove any acetamide which might be present. Removal of the hexane solvent under vacuum gave p-isobutylpropiophenone dimethyl ketal as a pale yellow oil which was used without further purification. The NMR was in accord. 3-necked, round-bottomed flask there was added a solution of 9.71 g reaction The resulting mixture was filtered to remove the precipitated ammonium chloride concentrated under vacuum Hexane (50 ml.) was added to the residue the resulting solution was again filtered to remove any acetamide which Removal of the hexane solvent under vacuum