ethyl 4-methoxy-3-oxobutanoate

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 15.8 g of ethyl 4-chloroacetoacetate (96.2 mmol) and 3.39 g of methanol (106 mmol) in 10 mL of THF were added dropwise to a stirred suspension of 4.62 g of 60% NaH (in mineral oil), 1.60 g of NaI (9.62 mmol), and 3.10 g of tetrabutylammonium bromide (9.62 mmol) in 40 mL of THF at −30° C. over a period of 1.5 hrs. The reaction mixture was then warmed to room temperature and stirred for 4 days. The reaction mixture was cooled to −30° C., quenched with 5 mL of methanol, and warmed to room temperature. The reaction mixture was poured into 0.5 L of 10% HCl solution, extracted with 2×100 mL of EtOAc, dried (Na2SO4), and the solvent was removed in vacuo. The crude product was distilled. The fraction boiling at 65-70° C. (0.3 mm Hg) was collected and used in the next experiments after spectral characterization. The reaction mixture was cooled to −30° C. quenched with 5 mL of methanol warmed to room temperature The reaction mixture was poured into 0.5 L of 10% HCl solution extracted with 2×100 mL of EtOAc dried (Na2SO4) the solvent was removed in vacuo The crude product was distilled The fraction boiling at 65-70° C. (0.3 mm Hg) was collected

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

Procedure: 7.6 g of 4-methylmercaptobenzaldehyde, 16 g of γ-methoxyacetoacetic acid ethyl ester and 6 ml of aqueous concentrated ammonia in 30 ml of ethanol are heated to the boil for 6-8 hours, and 2,6-dimethoxymethyl-4-(4'-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of beige crystals of melting point 136°-138° C.

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

Procedure: A solution of 9.2 g of 4-methylsulphonylbenzaldehyde, 8 g of γ-methoxyacetoacetic acid ethyl ester and 6.5 g of β-aminocrotonic acid ethyl ester in 40 ml of ethanol is heated to the boil and, after cooling, 2-methoxymethyl-6-methyl-4-(4'-methylsulphonylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of yellow crystals of melting point 156°-158° C. after cooling

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

Procedure: 8.7 g of 2-trifluoromethylbenzaldehyde, 16 g of γ-methoxyacetoacetic acid ethyl ester and 5 ml of aqueous concentrated ammonia in 30 ml of ethanol are heated to the boil overnight, the mixture is cooled and 2,6-dimethoxymethyl-4-(2'-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of light brown crystals of melting point 133°-134° C, in a yield of 60% of theory. the mixture is cooled

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

Procedure: A mixture of 15.8 g of ethyl 4-chloroacetoacetate (96.2 mmol) and 3.39 g of methanol (106 mmol) in 10 mL of THF were added dropwise to a stirred suspension of 4.62 g of 60% NaH (in mineral oil), 1.60 g of NaI (9.62 mmol), and 3.10 g of tetrabutylammonium bromide (9.62 mmol) in 40 mL of THF at -30° C. over a period of 1.5 hrs. The reaction mixture was then warmed to room temperature and stirred for 4 days. The reaction mixture was cooled to -30° C., quenched with 5 mL of methanol, and warmed to room temperature. The reaction mixture was poured into 0.5 L of 10% HCl solution, extracted with 2×100 mL of EtOAc, dried (Na2 SO4), and the solvent was removed in vacuo. The crude product was distilled. The fraction boiling at 65°-70° C. (0.3 mm Hg) was collected and used in the next experiments after spectral characterization. The reaction mixture was cooled to -30° C. quenched with 5 mL of methanol warmed to room temperature The reaction mixture was poured into 0.5 L of 10% HCl solution extracted with 2×100 mL of EtOAc dried (Na2 SO4) the solvent was removed in vacuo The crude product was distilled The fraction boiling at 65°-70° C. (0.3 mm Hg) was collected

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

Procedure: A mixture of 15.8 g of ethyl 4-chloroacetoacetate (96.2 mmol) and 3.39 g of methanol (106 mmol) in 10 mL of THF were added dropwise to a stirred suspension of 4.62 g of 60% NaH (in mineral oil), 1.60 g of NaI (9.62 mmol), and 3.10 g of tetrabutylammonium bromide (9.62 mmol) in 40 mL of THF at -30° C. over a period of 1.5 hrs. The reaction mixture was then warmed to room temperature and stirred for 4 days. The reaction mixture was cooled to -30° C., quenched with 5 mL of methanol, and warmed to room temperature. The reaction mixture was poured into 0.5 L of 10% HCl solution, extracted with 2×100 mL of EtOAc, dried (Na2 SO4), and the solvent was removed in vacuo. The crude product was distilled. The fraction boiling at 65°-70° C. (0.3 mm Hg) was collected and used in the next experiments after spectral characterization. The reaction mixture was cooled to -30° C. quenched with 5 mL of methanol warmed to room temperature The reaction mixture was poured into 0.5 L of 10% HCl solution extracted with 2×100 mL of EtOAc dried (Na2 SO4) the solvent was removed in vacuo The crude product was distilled The fraction boiling at 65°-70° C. (0.3 mm Hg) was collected

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

Procedure: 7.6 g of 4-methylmercaptobenzaldehyde, 16 g of γ-methoxyacetoacetic acid ethyl ester and 6 ml of aqueous concentrated ammonia in 30 ml of ethanol are heated to the boil for 6-8 hours, and 2,6-dimethoxymethyl-4-(4'-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of biege crystals of melting point 136°-138°C.

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

Procedure: 8.7 g of 2-trifluoromethylbenzaldehyde, 16 g of γ-methoxyacetoacetic acid ethyl ester and 5 ml of aqueous concentrated ammonia in 30 ml of ethanol are heated to the boil overnight, the mixture is cooled and 2,6-dimethoxymethyl-4-(2'-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of light brown crystals of melting point 133°-134°C, in a yield of 60% of theory. the mixture is cooled

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

Procedure: 8.7 g of 2-trifluoromethylbenzaldehyde, 16 g of γ-methoxyacetoacetic acid ethyl ester and 5 ml of aqueous concentrated ammonia in 30 ml of ethanol are heated to the boil overnight, the mixture is cooled and 2,6-dimethoxymethyl-4-(2'-trifluoromethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is obtained in the form of light brown crystals of melting point 133°-134°C, in a yield of 60% of theory. the mixture is cooled

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

Procedure: A solution of 2.69 g (10 mmol) 4-benzenesulphonyl-5-methylsulphanyl-2H-pyrazol-3-ylamine and 1.46 g (10 mmol) of ethyl 4-methoxy-acetoacetate in 10 ml of acetic acid was heated at reflux for 3 hrs. The reaction solution was evaporated and the residue was partitioned between H2O and CH2Cl2. The aqueous phase was extracted three times with 80 ml of CH2Cl2. The combined organic phases were dried (MgSO4), filtered and evaporated. Chromatography (SiO2, CH2Cl2/MeOH 25:1) yielded 3.1 g (85%) of 3-benzenesulphonyl-5-methoxymethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-ol as a beige powder, m.p. 175-155°. at reflux for 3 hrs The reaction solution was evaporated the residue was partitioned between H2O and CH2Cl2 The aqueous phase was extracted three times with 80 ml of CH2Cl2 The combined organic phases were dried (MgSO4) filtered evaporated

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

Procedure: A solution of 2.69 g (10 mmol) 4-benzenesulphonyl-5-methylsulphanyl-2H-pyrazol-3-ylamine and 1.46 g (10 mmol) of ethyl 4-methoxy-acetoacetate in 10 ml of acetic acid was heated at reflux for 3 hrs. The reaction solution was evaporated and the residue was partitioned between H2O and CH2Cl2. The aqueous phase was extracted three times with 80 ml of CH2Cl2. The combined organic phases were dried (MgSO4), filtered and evaporated. Chromatography (SiO2, CH2Cl2/MeOH 25:1) yielded 3.1 g (85%) of 3-benzenesulphonyl-5-methoxymethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-ol as a beige powder, m.p. 175-155°. at reflux for 3 hrs The reaction solution was evaporated the residue was partitioned between H2O and CH2Cl2 The aqueous phase was extracted three times with 80 ml of CH2Cl2 The combined organic phases were dried (MgSO4) filtered evaporated