ethyl 2-ethoxyacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the 2-methyl-1,3,4-oxadiazole (5.0 g, 59.5 mmol) in THF (100 mL) was added dropwise n-BuLi (23.79 mL, 59.5 mmol) in toluene under N2 at −78° C. After 1 h, ethyl ethoxyacetate (10.22 g, 77 mmol) was added. The reaction mixture was then allowed to warm to −40° C. and stirred for 2 h. The reaction mixture was then quenched with 65 mL of LON HCl and extracted with EtOAc. The organic layer was washed with water and then brine, dried over anhydrous Na2SO4, and concentrated. The resulting residue was purified on a flash chromatography column (Biotage™-40M) using a gradient of 0-100% of n-hexane/Et2O to give the desired product. 1H NMR (500 MHz, CD3OD): δ 1.27 (t, 3H), 2.64 (s, 3H), 3.69 (q, 2H), 4.88 (s, 2H). The reaction mixture was then quenched with 65 mL of LON HCl extracted with EtOAc The organic layer was washed with water brine, dried over anhydrous Na2SO4 concentrated The resulting residue was purified on a flash chromatography column (Biotage™-40M)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Benzyloxy)-3-methylbenzaldehyde (2.36 g; 10.2 mmole) and ethyl ethoxyacetate (1.62 g; 12.3 mmole) were dissolved in dry THF (10 ml) and cooled to −20° C. Potassium tert-butoxide (1.38 g; 12.3 mmole) dissolved in dry tetrahydrofuran (1 ml) was slowly added and the reaction was stirred over night at −20° C. The reaction was quenched with acetic acid (0.80 g; 13.3 mmole). The crude product was isolated, redissolved in toluene and refluxed overnight with p-toluenesulfonic acid (0.18 g; 1.0 mmole) in a Dean-Stark apparatus to separate the water. The solution was cooled, washed with sodium hydrogen carbonate, dried with magnesium sulfate and evaporated. Purification of the crude product with preparative HPLC (Kromasil C8, 10 μm, 50×500 mm) using acetronitrile (50-100%) in ammonium acetate buffer (pH 7) as mobile phase gave 0.86 g (25% yield) of ethyl (2Z)-3-[4-(benzyloxy)-3-methylphenyl]-2-ethoxyacrylate. was slowly added The crude product was isolated to separate the water The solution was cooled washed with sodium hydrogen carbonate dried with magnesium sulfate evaporated Purification of the crude product with preparative HPLC (Kromasil C8, 10 μm, 50×500 mm)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Benzyloxy)-3-nitrobenzaldehyde (4.12 g; 14.4 mmole) and ethyl ethoxyacetate (2.29 g; 17.3 mmole) were dissolved in dry tetrahydrofuran (20 ml) and cooled to −20° C. Potassium tert-butoxide (1.94 g; 17.3 mmole) dissolved in dry tetrahydrofuran (10 ml) was slowly added and the reaction was stirred overnight at −20° C. The reaction was quenched with acetic acid (1.3 g; 21.7 mmole). The crude product was isolated, redissolved in toluene and refluxed over night with p-toluenesulfonic acid (0.25 g; 1.44 mmole) in a Dean-Stark apparatus to separate the water. The solution was cooled, washed with sodium hydrogen carbonate, dried with magnesium sulfate and evaporated. Chromatography of the crude material from methylene chloride gave 0.85 g (11% yield) of ethyl (2Z)-3-[4-(benzyloxy)-3-nitrophenyl]-2-ethoxyacrylate. was slowly added The crude product was isolated to separate the water The solution was cooled washed with sodium hydrogen carbonate dried with magnesium sulfate evaporated

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Benzyloxy)-2-tert-butylbenzaldehyde (0.66 g; 2.44 mmole) and ethyl ethoxyacetate (0.39 g; 2.93 mmole) were dissolved in dry tetrahydrofuran (10 ml) and cooled to −20° C. Potassium tert-butoxide (0.33 g; 2.93 mmole) dissolved in dry tetrahydrofuran (1 ml) was slowly added and the reaction was stirred overnight at −20° C. The reaction was quenched with acetic acid (0.19 g; 3.18 mmole). The crude product was isolated, redissolved in toluene and refluxed over night with p-toluenesulfonic acid (0.05 g; 0.25 mmole) in a Dean-Stark apparatus to separate the water. The solution was cooled, washed with sodium hydrogen carbonate, dried with magnesium sulfate and evaporated. Purification of the crude product with preparative HPLC (Kromasil C8, 7 μm, 50×250 mm) using acetronitrile (50-100%) in ammonium acetate buffer (pH 7) as mobile phase gave 0.26 g (25% yield) of ethyl (2Z)-3-[4-(benzyloxy)-3-tert-butylphenyl]-2-ethoxyacrylate. was slowly added The crude product was isolated to separate the water The solution was cooled washed with sodium hydrogen carbonate dried with magnesium sulfate evaporated Purification of the crude product with preparative HPLC (Kromasil C8, 7 μm, 50×250 mm)

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

Procedure: In analogy to the procedure described in example 47 a], 4-benzyloxy-2-isopropoxy-benzaldehyde [Chemical & Pharmaceutical Bulletin (1998), 46(2), 222-230] was reacted with the enolate of ethyl ethoxyacetate, to yield [rac]-3-(4-benzyloxy-2-isopropoxy-phenyl)-2-ethoxy-3-hydroxy-propionic acid ethyl ester as a mixture of diastereomers in form of a light yellow oil.

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

Procedure: In analogy to the procedure described in example 47 a], 4-benzyloxy-2-isopropoxy-benzaldehyde [Chemical & Pharmaceutical Bulletin (1998), 46(2), 222-230] was reacted with the enolate of ethyl ethoxyacetate, to yield [rac]-3-(4-benzyloxy-2-isopropoxy-phenyl)-2-ethoxy-3-hydroxy-propionic acid ethyl ester as a mixture of diastereomers in form of a light yellow oil.

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl ethoxylacetate (20 g, 1.0 eq) and ethyl formate (11.21 ml, 1.0 eq) was added dropwise to a slurry of sodium ethoxide (10.3 g, 1.0 eq) in toluene (100 ml) in ice both. After dropping at room temperature and stirring overnight, the resulting solution was dried in vacuo. Then a mixture of residue, urea (9.09 g, 1.0 eq) and sodium ethoxide (10.3 g, 1.0 eq) in EtOH (100 ml) was refluxed at 110° C. for 6 hrs. After the solvent was dried in vacuo, water and conc. HCl solution (5<pH<4) were added. After formation of white precipitates, the mixture was filtered and dried solid in vacuo. A product was obtained as a white solid (7.76 g, 32%) After dropping at room temperature the resulting solution was dried in vacuo After the solvent was dried in vacuo, water and conc. HCl solution (5<pH<4) were added After formation of white precipitates, the mixture was filtered dried solid in vacuo

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl ethoxylacetate (20 g, 1.0 eq) and ethyl formate (11.21 ml, 1.0 eq) was added dropwise to a slurry of sodium ethoxide (10.3 g, 1.0 eq) in toluene (100 ml) in ice both. After dropping at room temperature and stirring overnight, the resulting solution was dried in vacuo. Then a mixture of residue, urea (9.09 g, 1.0 eq) and sodium ethoxide (10.3 g, 1.0 eq) in EtOH (100 ml) was refluxed at 110° C. for 6 hrs. After the solvent was dried in vacuo, water and conc. HCl solution (5<pH<4) were added. After formation of white precipitates, the mixture was filtered and dried solid in vacuo. A product was obtained as a white solid (7.76 g, 32%) After dropping at room temperature the resulting solution was dried in vacuo After the solvent was dried in vacuo, water and conc. HCl solution (5<pH<4) were added After formation of white precipitates, the mixture was filtered dried solid in vacuo