methyl 3-(2-hydroxyphenyl)propanoate

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: A mixture of 0.98 g (10 mmol) of 5-hexyn-1-ol, 1.98 g (11 mmol) of 2-hydroxybenzenepropanoic acid methyl ester, 2.88 g (11 mmol) of triphenylphosphine, 1.91 g (11 mmol) of diethyl azodicarboxylate, and 220 mL of dry tetrahydrofuran was stirred at room temperature for 100 hr and then concentrated under reduced pressure. The residue was triturated with 9:1 hexane-ether. The solid was filtered with suction and washed with the same solvent mixture. The filtrate and washes were combined and concentrated in vacuo. Flash chromatography of the residue on silica gel, eluting with 9:1 hexane-ether gave 2 g (77%) of 2[(5-hexynyl)oxy]benzenepropanoic acid methyl ester as a colorless oil. concentrated under reduced pressure The residue was triturated with 9:1 hexane-ether The solid was filtered with suction washed with the same solvent mixture concentrated in vacuo Flash chromatography of the residue on silica gel, eluting with 9:1 hexane-ether

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

Procedure: A mixture of 1.8 g (10 mmol) of 2-hydroxybenzenepropanoic acid methyl ester, 14 g (80 mmol) of α,α'-dichloro-m-xylene, 4.25 g (30.8 mmol) of anhydrous, granular potassium carbonate, and 70 mL of acetonitrile was stirred and refluxed for 4 hr. After being cooled, the resulting mixture was diluted with 200 mL of ether and filtered with suction. The solids were washed thoroughly with ether and then the filtrate and washes were combined and concentrated in vacuo. The oily residue was chromatographed on 100 g of silica gel. Elution with 19:1 hexane-ether afforded 1.74 g (54.6%) of 2-[3-(chloromethyl)phenylmethoxy]benzenepropanoic acid methyl ester as a colorless oil. refluxed for 4 hr After being cooled filtered with suction The solids were washed thoroughly with ether concentrated in vacuo The oily residue was chromatographed on 100 g of silica gel Elution with 19:1 hexane-ether

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

Procedure: A mixture of 3.6 g (20 mmol) of 2-hydroxybenzenepropanoic acid methyl ester, 22 mL (160 mmol) of 1,5-dibromopentane, 8.73 g (63.3 mmol) of anhydrous granular potassium carbonate, and 145 mL of acetonitrile was stirred and refluxed for 24 hr. The resulting slurry was cooled and diluted with 300 mL of ether. The solids were removed by suction filtration and the filter cake was washed well with ether. The filtrate and washes were combined and concentrated in vacuo giving 38.59 g of a brown oil which was chromatographed on 200 g of silica gel, eluting with 49:1 and 19:1 hexane-ether. The fractions containing the desired product were combined and concentrated giving 5.86 g of an oil which was dissolved in 50 mL of methanol containing 0.2 g of p-toluenesulfonic acid monohydrate. The solution was stirred at room temperature for 17 hr and refluxed for 5 hr before being cooled and concentrated in vacuo. The residue was dissolved in ether and the solution was washed with saturated sodium bicarbonate solution and worked-up in the usual manner. The oily residue was chromatographed on 100 g of silica gel. Elution with 19:1 hexane-ether afforded 4.85 g (73.7%) of 2-[5-bromopentyl)oxy]benzenepropanoic acid methyl ester as a colorless oil. refluxed for 24 hr The resulting slurry was cooled The solids were removed by suction filtration the filter cake was washed well with ether concentrated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 3-(hydroxyphenyl)propionate (15 g, 83.24 mmol) and iodopropane (12.14 mL, 124.5 mmol) in DMF (80 mL) was added K2CO3 (34 g, 249.7 mmol). The resultant slurry was stirred vigorously and heated to 60° C. under argon for 12 h. DMF was evaporated and residue partitioned between EtOAC and 1N HCl. The organic layer was washed with H2O, and brine then dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (10% EtOAc in hexanes) to provide the desired product (17 g, 98%) as a clear oil. The resultat oil was dissolved in THF (150 mL), and 2M NaOH (68 mL) was added. The reaction was stirred overnight at room temperature. THF was evaporated and residue acidified with concentrated HCl and extracted 3 times with EtOAC, (100 mL). The organic layer was washed with H2O, dried over Na2SO4 and concentrated to a white solid which was recrystalized from hexanes to provide the desired product (14.06 g 82%). DMF was evaporated residue partitioned between EtOAC and 1N HCl The organic layer was washed with H2O, and brine then dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (10% EtOAc in hexanes)

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

Procedure: Dry triethylamine (0.38 mL, 2.8 mmol) and methyl 3-(2-hydroxyphenyl)propanoate, 80 (0.5 g, 2.77 mmol) in dry ether (9.2 mL) were added dropwise to a solution of dry ether (5 mL) containing phosphorus oxychloride (0.25 mL, 2.8 mmol) at −78° C. under nitrogen. Following the addition, the reaction mixture was slowly allowed to warm to rt, and stirred for 1 h. The solvent was removed under reduced pressure to give crude product as an oil containing a significant amount of solid. the addition The solvent was removed under reduced pressure to give crude product as an oil containing a significant amount of solid

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

Procedure: Dry triethylamine (0.38 mL, 2.8 mmol) and methyl 3-(2-hydroxyphenyl)propanoate, 80 (0.5 g, 2.77 mmol) in dry ether (9.2 mL) were added dropwise to a solution of dry ether (5 mL) containing phosphorus oxychloride (0.25 mL, 2.8 mmol) at −78° C. under nitrogen. Following the addition, the reaction mixture was slowly allowed to warm to rt, and stirred for 1 h. The solvent was removed under reduced pressure to give crude product as an oil containing a significant amount of solid. the addition The solvent was removed under reduced pressure to give crude product as an oil containing a significant amount of solid

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

Procedure: Diethyl azodicarboxylate (4.2 ml, 26.4 mmol) was added to a mixture of 2-(tritylamino)ethanol (6.08 g, 20.0 mmol), methyl 3-(2-hydroxyphenyl)propionate (5.00 g, 26.4 mmol), triphenylphosphine (6.91 g, 30.5 mmol) and THF (90 ml) at room temperature under nitrogen, and the mixture was standing for 20 hours at room temperature. The solvent was removed in vacuum. The residue was purified on SiO2, eluting with ethyl acetate-hexane (1:15), to afford the titled product as a colorless oil. (5.88 g, 49%) The solvent was removed in vacuum The residue was purified on SiO2 eluting with ethyl acetate-hexane (1:15)

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

Procedure: Diethyl azodicarboxylate (4.2 ml, 26.4 mmol) was added to a mixture of 2-(tritylamino)ethanol (6.08 g, 20.0 mmol), methyl 3-(2-hydroxyphenyl)propionate (5.00 g, 26.4 mmol), triphenylphosphine (6.91 g, 30.5 mmol) and THF (90 ml) at room temperature under nitrogen, and the mixture was standing for 20 hours at room temperature. The solvent was removed in vacuum. The residue was purified on SiO2, eluting with ethyl acetate-hexane (1:15), to afford the titled product as a colorless oil. (5.88 g, 49%) The solvent was removed in vacuum The residue was purified on SiO2 eluting with ethyl acetate-hexane (1:15)

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

Procedure: A mixture of 0.98 g (10 mmol) of 5-hexyn-1-ol, 1.98 g (11 mmol) of 2-hydroxybenzenepropanoic acid methyl ester, 2.88 g (11 mmol) of triphenylphosphine, 1.91 g (11 mmol) of diethyl azodicarboxylate, and 220 mL of dry tetrahydrofuran was stirred at room temperature for 100 hr and then concentrated under reduced pressure. The residue was triturated with 9:1 hexane-ether. The solid was filtered with suction and washed with the same solvent mixture. The filtrate and washes were combined and concentrated in vacuo. Flash chromatography of the residue on silica gel, eluting with 9:1 hexane-ether gave 2 g (77%) of 2[(5-hexynyl)oxy]benzenepropanoic acid methyl ester as a colorless oil. concentrated under reduced pressure The residue was triturated with 9:1 hexane-ether The solid was filtered with suction washed with the same solvent mixture concentrated in vacuo Flash chromatography of the residue on silica gel, eluting with 9:1 hexane-ether