ethyl 2-(3-formylphenoxy)acetate

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: Ethyl 2-(3-formylphenoxy)acetate (20.8 g, 0.1 mol, Alfa Aesar) and 4′-hydroxy-3′-methylacetophenone (15.0 g, 0.1 mol, Indofine) were dissolved in 150 mL of methanol and 50 mL of water. The solution was cooled with an ice-water bath, to which was added potassium hydroxide (21.0 g, 0.375 mol). The reaction mixture was stirred overnight. The resulted mixture was poured on to 600 mL of ice-water, acidified to pH=4-5 with 1 N HCl, and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with water and brine (200 mL each), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained oil was dried under high-vacuum, 20 g (64%) of a solid was obtained as the desired (E)-2-(3-(3-(4-hydroxy-3-methylphenyl)-3-oxoprop-1-enyl)phenoxy)acetic acid. The solution was cooled with an ice-water bath, to which extracted with ethyl acetate (4×200 mL) The combined organic layers were washed with water and brine (200 mL each) dried over anhydrous sodium sulfate filtered concentrated in vacuo The obtained oil was dried under high-vacuum

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

Procedure: To a solution of 3-hydroxybenzaldehyde (10.0 g) and ethyl bromoacetate (15.0 g) in DMF (150 mL) was added potassium carbonate (17.0 g), and the mixture was stirred at 60° C. for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (16.7 g) as a colorless oil. the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: To a solution of 3-hydroxybenzaldehyde (10.0 g) and ethyl bromoacetate (15.0 g) in DMF (150 mL) was added potassium carbonate (17.0 g), and the mixture was stirred at 60° C. for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (16.7 g) as a colorless oil. the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: 3-Hydroxybenzaldehyde (2.00 g, 16.4 mmol) was dissolved in 25 mL of dry tetrahydrofuran under nitrogen with 3.5 g of potassium carbonate and 3.01 g (18.0 mmol) of ethyl bromoacetate. The reaction was heated at reflux for 6 hr, then cooled to room temperature and filtered from inorganic salts. The filtrate was evaporated, redissolved in 30 mL of methylene chloride, washed with 2×15 mL of water, and dried over sodium sulfate. Evaporation of solvent gave 2.92 of ethyl 3-formylphenoxyacetate as a yellow oil. The reaction was heated at reflux for 6 hr filtered from inorganic salts The filtrate was evaporated redissolved in 30 mL of methylene chloride washed with 2×15 mL of water dried over sodium sulfate Evaporation of solvent

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

Procedure: 3-Hydroxybenzaldehyde (2.00 g, 16.4 mmol) was dissolved in 25 mL of dry tetrahydrofuran under nitrogen with 3.5 g of potassium carbonate and 3.01 g (18.0 mmol) of ethyl bromoacetate. The reaction was heated at reflux for 6 hr, then cooled to room temperature and filtered from inorganic salts. The filtrate was evaporated, redissolved in 30 mL of methylene chloride, washed with 2×15 mL of water, and dried over sodium sulfate. Evaporation of solvent gave 2.92 of ethyl 3-formylphenoxyacetate as a yellow oil. The reaction was heated at reflux for 6 hr filtered from inorganic salts The filtrate was evaporated redissolved in 30 mL of methylene chloride washed with 2×15 mL of water dried over sodium sulfate Evaporation of solvent

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

Procedure: Ethyl 2-(3-formylphenoxy)acetate (20.8 g, 0.1 mol) and 4′-hydroxy-3′-methylacetophenone (15.0 g, 0.1 mol) were dissolved in 150 mL of methanol and 50 mL of water. The solution was cooled with an ice-water bath, to which was added potassium hydroxide (21.0 g, 0.375 mol). The reaction mixture was stirred overnight. The resulted mixture was poured on to 600 mL of ice-water, acidified to pH=4-5 with 1 N HCl, and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with water and brine (200 mL each), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained yellow oil was dried under high-vacuum, 20 g (64%) of yellowish solid was obtained. 1H NMR (400 MHz, CDCl3): δ 9.95 (s, 1H), 8.40 (br, 1H), 7.80 (s, 1H), 7.65 (m, 2H), 7.22-7.55 (m, 5H), 6.85 (d, 1H), 4.75 (s, 2H), 2.22 (s, 3H). MS (EI): 313 (MH+). The solution was cooled with an ice-water bath, to which extracted with ethyl acetate (4×200 mL) The combined organic layers were washed with water and brine (200 mL each) dried over anhydrous sodium sulfate filtered concentrated in vacuo The obtained yellow oil was dried under high-vacuum

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (3.54 g, 15.95 mmol), 3-(ethoxycarbonylmethoxy)benzaldehyde (4.3 g) and xylenes (20 ml) was heated at 160° C. overnight. The reaction mixture was cooled to room temperature, a solid formed which was collected by filtration and washed with methanol and then ether. The product was recrystallized from acetonitrile to afford 2.48 g of 1-cyclopentyl-3-ethyl-6-[3-(ethoxycarbonylmethoxy)phenyl]pyrazolo[3 4-d]pyrimidin-4-one. An additional 0.3 g of product was also obtained from the recrystallization of the filtrate for a total of 2.78 g. The reaction mixture was cooled to room temperature a solid formed which was collected by filtration washed with methanol The product was recrystallized from acetonitrile

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

Procedure: To a mixture of 3-hydroxybenzaldehyde (5.17 g, 42.34 mmol), K2CO3 (5.85 g) and acetone (50 ml) was added ethyl bromoacetate (5.2 ml). The reaction mixture was stirred at room temperature overnight, additional K2CO3 (1 equivalent) was added, the mixture was stirred for one hour, then additional ethyl bromoacetate (0.5 equivalents) was added and the mixture was stirred at room temperature until the reaction was complete. The reaction mixture was filtered, water was added to the filtrate and the solvent was removed. The residue was dissolved in ether, extracted with 1M NaOH (2×100 ml), and the ether layer was dried over MgSO4 and stripped to afford, as a liquid, 7.89 g of 3-(ethoxycarbonylmethoxy)benzaldehyde. the mixture was stirred for one hour the mixture was stirred at room temperature until the reaction The reaction mixture was filtered water was added to the filtrate the solvent was removed The residue was dissolved in ether extracted with 1M NaOH (2×100 ml) the ether layer was dried over MgSO4

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

Procedure: To a mixture of 3-hydroxybenzaldehyde (5.17 g, 42.34 mmol), K2CO3 (5.85 g) and acetone (50 ml) was added ethyl bromoacetate (5.2 ml). The reaction mixture was stirred at room temperature overnight, additional K2CO3 (1 equivalent) was added, the mixture was stirred for one hour, then additional ethyl bromoacetate (0.5 equivalents) was added and the mixture was stirred at room temperature until the reaction was complete. The reaction mixture was filtered, water was added to the filtrate and the solvent was removed. The residue was dissolved in ether, extracted with 1M NaOH (2×100 ml), and the ether layer was dried over MgSO4 and stripped to afford, as a liquid, 7.89 g of 3-(ethoxycarbonylmethoxy)benzaldehyde. the mixture was stirred for one hour the mixture was stirred at room temperature until the reaction The reaction mixture was filtered water was added to the filtrate the solvent was removed The residue was dissolved in ether extracted with 1M NaOH (2×100 ml) the ether layer was dried over MgSO4