methyl 2-(4-hydroxyphenyl)propanoate

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

Procedure: To a stirred solution of methyl 4-hydroxyphenylpropanoate (2.41 g, 13.4 mmol) and potassium carbonate (2.76 g, 20 mmol) in 75 mL of 2-butanone at ambient temperature was added in one portion of (bromomethyl)cyclopropane (2.72 g, 20 mmol). The stirred reaction mixture was heated at reflux for 18 hr. HPLC revealed the disappearance of the starting material of methyl 4-hydroxyphenylpropanoate. The mixture was allowed to cool to ambient temperature. The solid was filtered off. The filter cake was washed with acetone. The combined filtrate was concentrated in vacuo to nearly dryness. Methanol was added (10 mL) was added to the residue, followed by the addition of a 2-N aqueous solution of NaOH (25 mL, 50 mmol). The reaction was stirred overnight at about 40° C. HPLC indicated that the saponification was completed, and revealed one single peak signal of the expected carboxylic acid. The reaction mixture was subjected to roto-vaporation to remove methanol. Ice was added to the basic aqueous solution. The acidification with a 30 mL of HCl aqueous 2N solution (60 mmol) led to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane. The collected solid was dried in vacuo for two days at ambient temperature to afford 1.77 g (60%) of 3-[4-(cyclopropylmethoxy)phenyl]propanoic acid as a white solid. The stirred reaction mixture was heated at reflux for 18 hr The solid was filtered off The filter cake was washed with acetone The combined filtrate was concentrated in vacuo to nearly dryness Methanol was added (10 mL) was added to the residue to remove methanol Ice was added to the basic aqueous solution Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane The collected solid was dried in vacuo for two days at ambient temperature

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

Procedure: In a mixture of 18ml of nitric acid and 30ml of acetic acid 2.76g of methyl 2-(4-hydroxyphenyl)propionate was stirred at -10° to -20° C for 4 hours. The reaction mixture was poured into ice water and extracted with chloroform. The extract was washed with a sodium hydrogen carbonate solution and water and dried over magnesium sulfate. The chloroform was distilled off to give the desired compound in a yield of 2.35g (69%). The physical data of this compound coincided with those of the compound as described above. extracted with chloroform The extract was washed with a sodium hydrogen carbonate solution and water dried over magnesium sulfate The chloroform was distilled off

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

Procedure: In a mixture of 12ml of hydroiodic acid, 90ml of acetic acid and 1g of phosphorus 10g of 2-(4-methoxyphenyl)propionic acid was refluxed for 3 hours and the reaction mixture was concentrated. 20ml of methanol and 2ml of sulfuric acid were added to the residue and the mixture was refluxed for one hour. After the methanol was concentrated, the water was added to the residue and extracted with ether. The extract was washed over magnesium sulfate and the ether was distilled off. The residue was distilled under reduced pressure to give the object compound having b.p. 150° - 153° C/6mm Hg in a yield of 6.7g (67%) was refluxed for 3 hours the reaction mixture was concentrated 20ml of methanol and 2ml of sulfuric acid were added to the residue the mixture was refluxed for one hour After the methanol was concentrated the water was added to the residue extracted with ether The extract was washed over magnesium sulfate the ether was distilled off The residue was distilled under reduced pressure to give the object compound

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of Example 46A (2.6 g, 12 mmol) in anhydrous dimethylformamide (20 mL) was treated with potassium carbonate (3.3 g, 24 mmol) and allyl bromide (1.2 mL, 13 mmol), and reaction heated for 16 hours at 80° C. Reaction mixture cooled and diluted with ethyl acetate. Mixture washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane to provide the title compound. Reaction mixture cooled Mixture washed with water and brine dried (Na2SO4) filtered concentrated under reduced pressure Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of Example 46A (2.6 g, 12 mmol) in anhydrous dimethylformamide (20 mL) was treated with potassium carbonate (3.3 g, 24 mmol) and allyl bromide (1.2 mL, 13 mmol), and reaction heated for 16 hours at 80° C. Reaction mixture cooled and diluted with ethyl acetate. Mixture washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane to provide the title compound. Reaction mixture cooled Mixture washed with water and brine dried (Na2SO4) filtered concentrated under reduced pressure Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of Example 46A (2.6 g, 12 mmol) in anhydrous dimethylformamide (20 mL) was treated with potassium carbonate (3.3 g, 24 mmol) and allyl bromide (1.2 mL, 13 mmol), and reaction heated for 16 hours at 80° C. Reaction mixture cooled and diluted with ethyl acetate. Mixture washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane to provide the title compound. Reaction mixture cooled Mixture washed with water and brine dried (Na2SO4) filtered concentrated under reduced pressure Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane

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

Procedure: To a stirred solution of methyl 4-hydroxyphenylpropanoate (2.41 g, 13.4 mmol) and potassium carbonate (2.76 g, 20 mmol) in 75 mL of 2-butanone at ambient temperature was added in one portion of (bromomethyl)cyclopropane (2.72 g, 20 mmol). The stirred reaction mixture was heated at reflux for 18 hr. HPLC revealed the disappearance of the starting material of methyl 4-hydroxyphenylpropanoate. The mixture was allowed to cool to ambient temperature. The solid was filtered off. The filter cake was washed with acetone. The combined filtrate was concentrated in vacuo to nearly dryness. Methanol was added (10 mL) was added to the residue, followed by the addition of a 2-N aqueous solution of NaOH (25 mL, 50 mmol). The reaction was stirred overnight at about 40° C. HPLC indicated that the saponification was completed, and revealed one single peak signal of the expected carboxylic acid. The reaction mixture was subjected to roto-vaporation to remove methanol. Ice was added to the basic aqueous solution. The acidification with a 30 mL of HCl aqueous 2N solution (60 mmol) led to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane. The collected solid was dried in vacuo for two days at ambient temperature to afford 1.77 g (60%) of 3-[4-(cyclopropylmethoxy)phenyl]propanoic acid as a white solid. The stirred reaction mixture was heated at reflux for 18 hr The solid was filtered off The filter cake was washed with acetone The combined filtrate was concentrated in vacuo to nearly dryness Methanol was added (10 mL) was added to the residue to remove methanol Ice was added to the basic aqueous solution Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane The collected solid was dried in vacuo for two days at ambient temperature

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

Procedure: In a mixture of 18ml of nitric acid and 30ml of acetic acid 2.76g of methyl 2-(4-hydroxyphenyl)propionate was stirred at -10° to -20° C for 4 hours. The reaction mixture was poured into ice water and extracted with chloroform. The extract was washed with a sodium hydrogen carbonate solution and water and dried over magnesium sulfate. The chloroform was distilled off to give the desired compound in a yield of 2.35g (69%). The physical data of this compound coincided with those of the compound as described above. extracted with chloroform The extract was washed with a sodium hydrogen carbonate solution and water dried over magnesium sulfate The chloroform was distilled off

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

Procedure: In a mixture of 18ml of nitric acid and 30ml of acetic acid 2.76g of methyl 2-(4-hydroxyphenyl)propionate was stirred at -10° to -20° C for 4 hours. The reaction mixture was poured into ice water and extracted with chloroform. The extract was washed with a sodium hydrogen carbonate solution and water and dried over magnesium sulfate. The chloroform was distilled off to give the desired compound in a yield of 2.35g (69%). The physical data of this compound coincided with those of the compound as described above. extracted with chloroform The extract was washed with a sodium hydrogen carbonate solution and water dried over magnesium sulfate The chloroform was distilled off

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

Procedure: In a mixture of 12ml of hydroiodic acid, 90ml of acetic acid and 1g of phosphorus 10g of 2-(4-methoxyphenyl)propionic acid was refluxed for 3 hours and the reaction mixture was concentrated. 20ml of methanol and 2ml of sulfuric acid were added to the residue and the mixture was refluxed for one hour. After the methanol was concentrated, the water was added to the residue and extracted with ether. The extract was washed over magnesium sulfate and the ether was distilled off. The residue was distilled under reduced pressure to give the object compound having b.p. 150° - 153° C/6mm Hg in a yield of 6.7g (67%) was refluxed for 3 hours the reaction mixture was concentrated 20ml of methanol and 2ml of sulfuric acid were added to the residue the mixture was refluxed for one hour After the methanol was concentrated the water was added to the residue extracted with ether The extract was washed over magnesium sulfate the ether was distilled off The residue was distilled under reduced pressure to give the object compound

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

Procedure: In a mixture of 12ml of hydroiodic acid, 90ml of acetic acid and 1g of phosphorus 10g of 2-(4-methoxyphenyl)propionic acid was refluxed for 3 hours and the reaction mixture was concentrated. 20ml of methanol and 2ml of sulfuric acid were added to the residue and the mixture was refluxed for one hour. After the methanol was concentrated, the water was added to the residue and extracted with ether. The extract was washed over magnesium sulfate and the ether was distilled off. The residue was distilled under reduced pressure to give the object compound having b.p. 150° - 153° C/6mm Hg in a yield of 6.7g (67%) was refluxed for 3 hours the reaction mixture was concentrated 20ml of methanol and 2ml of sulfuric acid were added to the residue the mixture was refluxed for one hour After the methanol was concentrated the water was added to the residue extracted with ether The extract was washed over magnesium sulfate the ether was distilled off The residue was distilled under reduced pressure to give the object compound

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of Example 46A (2.6 g, 12 mmol) in anhydrous dimethylformamide (20 mL) was treated with potassium carbonate (3.3 g, 24 mmol) and allyl bromide (1.2 mL, 13 mmol), and reaction heated for 16 hours at 80° C. Reaction mixture cooled and diluted with ethyl acetate. Mixture washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane to provide the title compound. Reaction mixture cooled Mixture washed with water and brine dried (Na2SO4) filtered concentrated under reduced pressure Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane