ethyl 2-methoxyacetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of [3,4-bis(methyloxy)phenyl]acetonitrile (2.0 g, 11 mmol) and ethyl (methyloxy)acetate (1.65 g, 14 mmol) in ethanol (4 mL) was added a sodium ethoxide solution (21%, 8.4 mL, 23 mmol), and the resulting mixture was heated at reflux for 18 hours. After cooling to room temperature, it was poured into a mixture of ice-water (50 mL). This aqueous mixture was washed with dichloromethane (3×20 mL) to remove all non-basic organic impurities, and then it was acidified to pH of 1. The acidified mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with aqueous sodium bicarbonate solution, brine, dried over sodium sulfate, filtered and concentrated to give 2-[3,4-bis(methyloxy)phenyl]-4-(methyloxy)-3-oxobutanenitrile as a brown oil (1.8 g, 7.2 mmol, 66% yield), MS (EI) for C13H15NO4: 250 (MH+). the resulting mixture was heated at reflux for 18 hours This aqueous mixture was washed with dichloromethane (3×20 mL) to remove all non-basic organic impurities The acidified mixture was extracted with ethyl acetate (3×30 mL) The combined extract was washed with aqueous sodium bicarbonate solution, brine dried over sodium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of [3,4-bis(methyloxy)phenyl]acetonitrile (2.0 g, 11 mmol) and ethyl (methyloxy)acetate (1.65 g, 14 mmol) in ethanol (4 mL) was added a sodium ethoxide solution (21%, 8.4 mL, 23 mmol), and the resulting mixture was heated at reflux for 18 hours. After cooling to room temperature, it was poured into a mixture of ice-water (50 mL). This aqueous mixture was washed with dichloromethane (3×20 mL) to remove all non-basic organic impurities, and then it was acidified to pH of 1. The acidified mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with aqueous sodium bicarbonate solution, brine, dried over sodium sulfate, filtered and concentrated to give 2-[3,4-bis(methyloxy)phenyl]-4-(methyloxy)-3-oxobutanenitrile as a brown oil (1.8 g, 7.2 mmol, 66% yield), MS (EI) for C13H15NO4: 250 (MH+). the resulting mixture was heated at reflux for 18 hours This aqueous mixture was washed with dichloromethane (3×20 mL) to remove all non-basic organic impurities The acidified mixture was extracted with ethyl acetate (3×30 mL) The combined extract was washed with aqueous sodium bicarbonate solution, brine dried over sodium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred refluxing solution of sodium ethoxide (from 1.38 g sodium) in ethanol (25 ml) was added over 5 minutes a mixture of 2,3,5-trichlorophenylacetonitrile (11 g) and ethyl methoxyacetate (8.85 g) in dry DME (25 ml). After 4 hours the mixture was cooled on ice and acidified by dropwise addition of acetic acid (ca. 6 ml), diluted with ice-water (150 ml) and extracted with dichloromethane (2×100 ml). The dichloromethane extract was washed with water, dried over MgSO4 and concentrated giving a yellow solid, which was triturated with a little ether and filtered. 8.6 g Homogeneous by TLC (19:1 CH2Cl2 :MeOH). was added over 5 minutes After 4 hours the mixture was cooled on ice extracted with dichloromethane (2×100 ml) The dichloromethane extract was washed with water dried over MgSO4 concentrated giving a yellow solid, which was triturated with a little ether filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred refluxing solution of sodium ethoxide (from 1.38 g sodium) in ethanol (25 ml) was added over 5 minutes a mixture of 2,3,5-trichlorophenylacetonitrile (11 g) and ethyl methoxyacetate (8.85 g) in dry DME (25 ml). After 4 hours the mixture was cooled on ice and acidified by dropwise addition of acetic acid (ca. 6 ml), diluted with ice-water (10 ml) and extracted with dichloromethane (2×100 ml). The dichloromethane extract was washed with water, dried over MgSO4 and concentrated giving a yellow solid, which was triturated with a little ether and filtered. 8.6 g Homogeneous by TLC (19:1 CH2Cl2 :MeOH). was added over 5 minutes After 4 hours the mixture was cooled on ice extracted with dichloromethane (2×100 ml) The dichloromethane extract was washed with water dried over MgSO4 concentrated giving a yellow solid, which was triturated with a little ether filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred refluxing solution of sodium ethoxide (from 1.38 g sodium) in ethanol (25 ml) was added over 5 minutes a mixture of 2,3,5-trichlorophenylacetonitrile (11 g) and ethyl methoxyacetate (8.85 g) in dry DME (25 ml). After 4 hours the mixture was cooled on ice and acidified by dropwise addition of acetic acid (ca. 6 ml), diluted with ice-water (150 ml) and extracted with dichloromethane (2×100 ml). The dichloromethane extract was washed with water, dried over MgSO4 and concentrated giving a yellow solid, which was triturated with a little ether and filtered. 8.6 g Homogeneous by TLC (19:1 CH2Cl2 :MeOH). was added over 5 minutes After 4 hours the mixture was cooled on ice extracted with dichloromethane (2×100 ml) The dichloromethane extract was washed with water dried over MgSO4 concentrated giving a yellow solid, which was triturated with a little ether filtered

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of sodium hyride (0.63 g) in THF (65 ml) was treated with the compound of Example 77 (4.0 g) and heated at 60° C. for 3 hours. Ethyl bromoacetate (10.9 g) was added to the cooled mixture and the reaction was allowed to proceed at ambient temperature overnight. The crude methoxy acetic acid ethyl ester was poured into ethanol (200 ml), treated with 3N sodium hydroxide and heated at reflux temperature for 1.5 hours. The solution was concentrated to 100 ml, diluted to 250 ml with water and unreacted compound of Example 77 extracted into ethyl acetate. The aqueous phase was acidified and crude product filtered. Ethanol crystallization gave the title compound (2.18 g, m.p. 123° C.). An analytical sample, m.p. 183° C., was obtained from ethanol solution. heated at reflux temperature for 1.5 hours The solution was concentrated to 100 ml diluted to 250 ml with water and unreacted compound of Example 77 extracted into ethyl acetate crude product filtered Ethanol crystallization

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 50 ml of benzene was suspended 2.5 g of 60% sodium hydride. While cooling the suspension, a mixture of 5.6 g of 4-methylcyclohexanone and 5.4 g of ethyl methoxyacetate was dropwise added thereto. After stirring at room temperature for 2 hours, 20 ml of water was added thereto and the pH was rendered 3 with concentrated hyrochloric acid. The benzene phase was separated and the aqueous phase was extracted with ether. The benzene solution and the ether solution were combined with each other followed by washing with a sodium chloride aqueous solution. After drying, the mixture was concentrated to give 7.4 g of crude 2-methoxyacetyl-4-methylcyclohexanone. The crude product was used at the following step. (2) 4-Cyano-2,3,5,6,7,8-hexahydro-1-methoxymethyl-7-methyl-3-oxoisoquinoline While cooling the suspension was dropwise added The benzene phase was separated the aqueous phase was extracted with ether by washing with a sodium chloride aqueous solution After drying the mixture was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred refluxing solution of sodium ethoxide (from 1.38 g sodium) in ethanol (25 ml) was added over 5 minutes a mixture of 2,3,5-trichlorophenylacetonitrile (11 g) and ethyl methoxyacetate (8.85 g) in dry DME (25 ml). After 4 hours the mixture was cooled on ice and acidified by dropwise addition of acetic acid (ca. 6 ml), diluted with ice-water (150 ml) and extracted with dichloromethane (2×100 ml). The dichloromethane extract was washed with water, dried over MgSO4 and concentrated giving a yellow solid, which was triturated with a little ether and filtered. 8.6 g Homogeneous by TLC (19:1 CH2Cl2 :MeOH). was added over 5 minutes After 4 hours the mixture was cooled on ice extracted with dichloromethane (2×100 ml) The dichloromethane extract was washed with water dried over MgSO4 concentrated giving a yellow solid, which was triturated with a little ether filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of sodium (5.83 g, 243.3 mmol) in dry toluene (62.5 mL) was added ethyl (methyloxy)acetate (24 g, 203.4 mmol) at −5° C. After stirring for 3 h, acetone (14 g, 231.4 mmol) was slowly added, upon which the mixture became brown and viscous. Next added 72 mL of tert-butyl methyl ether, and the reaction mixture was stirred at room temperature for 12 h, after which time the sodium salt precipitated. After collection and washing with additional tert-butyl methyl ether, the sodium salt was dissolved in 46 mL of 20% H2SO4. The contents were extracted with tert-butyl methyl ether and the organic layers concentrated to afford 1-(methyloxy)-2,4-pentanedione (9.76 g, 36.9%). 1H NMR (400 MHz, CDCl3-d3) δ 5.76 (s, 1H), 3.96 (s, 2H), 3.38 (s, 3H), 2.07 (s, 3H). the reaction mixture was stirred at room temperature for 12 h after which time the sodium salt precipitated After collection washing with additional tert-butyl methyl ether the sodium salt was dissolved in 46 mL of 20% H2SO4 The contents were extracted with tert-butyl methyl ether the organic layers concentrated