magnesium;ethanolate

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

Procedure: To a stirred solution of tert-butyl 3-cyclopropyl-3-oxopropionate (9.2 g) in ethyl ether (200 mL) was added magnesium ethoxide (5.7 g). The reaction mixture was heated at reflux for 1 hour. After cooling back to room temperature, a solution of 2-methyl-3-ethoxy-4-methylsulfonylbenzoyl chloride (13.8 g), which was prepared from 2-methyl-3-ethoxy-4-methylsulfonylbenzoic acid (the preparation of which is described in U.S. Pat. No. 5,329,041 which is incorporated herein by reference) and oxalyl chloride, in ethyl ether (50 mL) was added over a period of 15 minutes. After stirring overnight at room temperature, the reaction mixture was poured over ice-water (100 mL), and the phases were separated. The ether layer was dried over magnesium sulfate and then concentrated in vacuo to afford 17 g of the crude product as an oil. The reaction mixture was heated at reflux for 1 hour the preparation of which the phases were separated The ether layer was dried over magnesium sulfate concentrated in vacuo

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

Procedure: In 200 mL of methanol, was dissolved 8.91 g (75.4 mmol) of monomethyl malonate, and the resulting solution was mixed with 4.30 g (37.5 mmol) of magnesium ethoxide, and stirred for 4 hours at room temperature. The reaction solution was concentrated and the residue was dried under reduced pressure. In 120 mL of tetrahydrofuran, was dissolved 4.10 mL (37.7 mmol) of cyclopentanecarboxylic acid, and the resulting solution was mixed with 6.69 g (41.2 mmol) of carbonyldiimidazole, followed by stirring for 2.5 hours. The reaction solution was added to a dry magnesium salt and the resulting mixture was stirred at room temperature for 221 hours. The reaction solution was concentrated; the residue was mixed with 150 mL of 2 N hydrochloric acid, extracted with ethyl acetate, and washed with an aqueous sodium hydrogencarbonate solution and then saturated sodium chloride water. The resultant was dried over sodium sulfate anhydride, filtered, and concentrated. The residue was distilled (0.15 mmHg, 51 to 55° C.) to give 5.72 g (33.4 mmol, 88.8%) of methyl 2-cyclopentanecarbonylacetate as an anhydrous liquid. Similarly to Example 133, 2.32 g (8.39 mmol, 57.0%) of pale yellow crystals were obtained from 5.72 g (33.4 mmol) of methyl 2-cyclopentanecarbonylacetate. The reaction solution was concentrated the residue was dried under reduced pressure by stirring for 2.5 hours the resulting mixture was stirred at room temperature for 221 hours The reaction solution was concentrated the residue was mixed with 150 mL of 2 N hydrochloric acid extracted with ethyl acetate washed with an aqueous sodium hydrogencarbonate solution The resultant was dried over sodium sulfate anhydride filtered concentrated The residue was distilled (0.15 mmHg, 51 to 55° C.)

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

Procedure: In 200 mL of methanol, was dissolved 8.90 g (75.4 mmol) of monomethyl malonate, and the resulting solution was mixed with 4.30 g (37.5 mmol) of magnesium ethoxide, followed by stirring for 4 hours at room temperature. The reaction solution was concentrated and the residue was dried under reduced pressure. In 150 mL of tetrahydrofuran, was dissolved 4.80 g (37.5 mmol) of 2-thiophenecarboxylic acid and the resulting solution was mixed with 6.69 g (41.2 mmol) of carbonyldiimidazole, followed by stirring for 1 hour. The reaction solution was added to a dry magnesium salt and stirred at room temperature for 21 hours. The reaction solution was concentrated; the residue was mixed with 150 mL of 1.5 N hydrochloric acid, extracted with ethyl acetate, and washed with an aqueous sodium hydrogencarbonate solution and then saturated sodium chloride water. The resultant was dried over sodium sulfate anhydride, filtered, and concentrated. The residue was distilled (0.06 mmHg, 87) to give 5.95 g (32.3 mmol, 86.1%) of methyl 2-thiophenecarbonylacetate as an anhydrous liquid. Similarly to Example 133, 2.52 g (8.28 mmol, 81.2%) of yellow crystals were obtained from 5.95 g (32.2 mmol) of methyl 2-thiophenecarbonylacetate by recrystallization from methanol. The reaction solution was concentrated the residue was dried under reduced pressure by stirring for 1 hour stirred at room temperature for 21 hours The reaction solution was concentrated the residue was mixed with 150 mL of 1.5 N hydrochloric acid extracted with ethyl acetate washed with an aqueous sodium hydrogencarbonate solution The resultant was dried over sodium sulfate anhydride filtered concentrated The residue was distilled (0.06 mmHg, 87)

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

Procedure: In 100 mL of methanol, was dissolved 5.90 g (50.0 mmol) of monomethyl malonate, and the resulting solution was mixed with 2.86 g (25 mmol) of magnesium ethoxide followed by stirring at room temperature for 4 hours. The reaction solution was concentrated and the residue was dried under reduced pressure. In 100 mL of tetrahydrofuran, was dissolved 2.80 g (25 mmol) of 2-furancarboxylic acid and the resulting solution was mixed with 4.45 g (27.4 mmol) of carbonyldiimidazole, followed by stirring for 1 hour. The reaction solution was added to a dry magnesium salt and stirred at room temperature for 19 hours. The reaction solution was concentrated; the residue was mixed with 100 mL of 1.5 N hydrochloric acid, extracted with ethyl acetate, and washed with an aqueous sodium hydrogencarbonate solution and saturated sodium chloride water. The resultant was dried over sodium sulfate anhydride, filtered, and concentrated. The residue was distilled (0.06 mmHg, 69 to 75) to give 2.93 g (17.4 mmol, 69.6%) of methyl 2-furancarbonylacetate as an anhydrous liquid. Similarly to Example 133, 65 mg (1.34 mmol, 58.1%) of dark yellow crystals were obtained from 2.93 g (17.4 mmol) of methyl 2-furancarbonylacetate. The reaction solution was concentrated the residue was dried under reduced pressure by stirring for 1 hour stirred at room temperature for 19 hours The reaction solution was concentrated the residue was mixed with 100 mL of 1.5 N hydrochloric acid extracted with ethyl acetate washed with an aqueous sodium hydrogencarbonate solution and saturated sodium chloride water The resultant was dried over sodium sulfate anhydride filtered concentrated The residue was distilled (0.06 mmHg, 69 to 75)

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

Procedure: One gram (5 mmoles) of aluminum isopropoxide was dissolved in 10 ml of Freon TF solvent and 0.7 grams (6 mmoles) of magnesium ethoxide added. After mixing in an ultra-sonic bath, followed by settling of suspended matter, 3 ml of the clear solution was analyzed for Mg and Al. Theory Al: 1.5 mmole, Found Al: 1.5 mmole. Theory Mg: 1.8 mmoles, Found Mg: 0.08 mmoles. Conclusion: Little effect of Aluminum alkoxide on solubility of Magnesium alkoxide in Freon TF, and therefore not a useful system for deacidification of books. added After mixing in an ultra-sonic bath

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

Procedure: One gram (5 mmoles) of aluminum isopropoxide was dissolved in 10 ml of Freon TF solvent and 0.7 grams (6 mmoles) of magnesium ethoxide added. After mixing in an ultra-sonic bath, followed by settling of suspended matter, 3 ml of the clear solution was analyzed for Mg and Al. Theory Al: 1.5 mmole, Found Al: 1.5 mmole. Theory Mg: 1.8 mmoles, Found Mg: 0.08 mmoles. Conclusion: Little effect of Aluminum alkoxide on solubility of Magnesium alkoxide in Freon TF, and therefore not a useful system for deacidification of books. added After mixing in an ultra-sonic bath

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Then, acetoacetate t-butyl ester in an amount of 8.9 g (56 mmol) was added into 80 ml toluene solution containing magnesium ethylate in an amount of 6.4 g (56 mmol) and the resulting mixture was stirred for 2 hours at 80° C., cooled down to an ambient temperature and added dropwise with 15 ml toluene solution of 3,6-dimethyl-2-nitrobenzoyl chloride in an amount of 10.3 g. The obtained mixture was stirred for 2 hours under heating and reflux, added with 10% sulfuric acid and extracted with ethyl acetate. The resulting organic solvent layer was washed with water and dried with anhydrous magnesium sulfate, and the solvent therein was distillated out under reduced pressure. The residue obtained was dissolved in 100 ml benzene and added with p-toluene sulfonic acid in an amount of 4.9 g (26 mmol), and the mixture was stirred for 2 hours under heating and reflux. Then, the reacted solution was washed with water and dried with anhydrous magnesium sulfate, and the solvent in the reacted solution was distillated out under reduced pressure. The residue obtained was purified by means of silica gei column chromatography to obtain 3,6-dimethyl-2-nitrobenzoylacetone in an amount of 3.9 g. cooled down to an ambient temperature The obtained mixture was stirred for 2 hours under heating reflux extracted with ethyl acetate The resulting organic solvent layer was washed with water dried with anhydrous magnesium sulfate The residue obtained the mixture was stirred for 2 hours under heating reflux Then, the reacted solution was washed with water dried with anhydrous magnesium sulfate The residue obtained was purified by means of silica gei column chromatography

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20-L reaction vessel was charged with magnesium ethoxide (3.61 moles; 413.52 g) and THF (6.6 L), and the resulting mixture was stirred as ethyl hydrogen malonate (7.23 moles; 888.89 mL; 994.67 g; diluted with 20 mL of THF) was added and the mixture was heated at 45° C. for 4 hours. Meanwhile, a 20 L reactor was charged with 2,5-dimethoxybenzoic acid (3.29 moles; 600.00 g) and THF (3.6 L). To this mixture stirring at room temperature was added 1,1′-carbonyldiimidazole (3.61 moles; 585.98 g) in portions to avoid excess foaming. After stirring for 3 hours at room temperature the second solution was added gradually to the first solution. After addition the reaction mixture was heated to 45° C. After 20 hours, the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (6 L) followed by 2 N HCl (3 L). After mixing, the layers were separated and the organic phase was washed sequentially with 2 N HCl (3 L), saturated sodium bicarbonate (3 L), and water (3 L). The organic phase was concentrated under reduced pressure, the residue taken up in ethyl acetate (6 L) and concentrated again to afford an oil, which was transferred to a 20 L reaction vessel with 5 L of ethyl acetate and treated with sodium methoxide (3.45 moles; 793.00 mL of a 4.35 M solution in methanol). After stirring at room temperature for 3 hours, an additional 6 L of ethyl acetate was added and the solid collected by vacuum filtration and dried overnight in a vacuum oven at 40° C. to give 661 grams of the title product. MS (ES+) 253.1 [M+1]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.92 (d, J=3.0 Hz, 1 H) 6.84 (d, J=8.8 Hz, 1 H) 6.73 (dd, J=8.8, 3.0 Hz, 1 H) 4.67 (s, 1 H) 3.88 (q, J=7.0 Hz, 2 H) 3.67 (s, 6 H) 1.12 (t, J=7.0 Hz, 3 H). was added After stirring for 3 hours at room temperature the second solution was added gradually to the first solution After addition the reaction mixture was heated to 45° C the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (6 L) After mixing the layers were separated the organic phase was washed sequentially with 2 N HCl (3 L), saturated sodium bicarbonate (3 L), and water (3 L) The organic phase was concentrated under reduced pressure concentrated again to afford an oil, which After stirring at room temperature for 3 hours the solid collected by vacuum filtration dried overnight in a vacuum oven at 40° C.

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 3000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with magnesium ethoxide (67.46 g, 589.51 mmoles) and THF (1100 mL), and the resulting mixture was stirred as ethyl hydrogen malonate (162.26 g, 1.18 moles; 145.00 mL diluted in 100 ml of THF) was added and the mixture was heated at 45° C. for 4 hours. Meanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with 5-chloro-2-methoxybenzoic acid (100 g, 536 mmoles) and THF (600 mL). To this mixture stirring at room temperature was added 1,1′-carbonyldiimidazole (95.59 g, 589.5 mmoles) in portions to avoid excess foaming. After stirring for 3 hours at room temperature the second solution was added gradually to the first solution. After addition the reaction mixture was heated to 45° C. After 20 hours, the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (1 L) followed by 2 N HCl (500 mL). After mixing, the layers were separated and the organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL). The organic phase was concentrated under reduced pressure, the residue taken up in ethyl acetate (1000 mL) and concentrated again to afford the title compound (104.94 g). A 3000 mL 3-necked round-bottomed flask flushed with nitrogen was added Meanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen After stirring for 3 hours at room temperature the second solution was added gradually to the first solution After addition the reaction mixture was heated to 45° C the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (1 L) After mixing the layers were separated the organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL) The organic phase was concentrated under reduced pressure concentrated again

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 3000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with magnesium ethoxide (67.46 g, 589.51 mmoles) and THF (1100 mL), and the resulting mixture was stirred as ethyl hydrogen malonate (162.26 g, 1.18 moles; 145.00 mL diluted in 100 ml of THF) was added and the mixture was heated at 45° C. for 4 hours. Meanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with 5-chloro-2-methoxybenzoic acid (100 g, 536 mmoles) and THF (600 mL). To this mixture stirring at room temperature was added 1,1′-carbonyldiimidazole (95.59 g, 589.5 mmoles) in portions to avoid excess foaming. After stirring for 3 hours at room temperature the second solution was added gradually to the first solution. After addition the reaction mixture was heated to 45° C. After 20 hours, the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (1 L) followed by 2 N HCl (500 mL). After mixing, the layers were separated and the organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL). The organic phase was concentrated under reduced pressure, the residue taken up in ethyl acetate (1000 mL) and concentrated again to afford the title compound (104.94 g). A 3000 mL 3-necked round-bottomed flask flushed with nitrogen was added Meanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen After stirring for 3 hours at room temperature the second solution was added gradually to the first solution After addition the reaction mixture was heated to 45° C the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (1 L) After mixing the layers were separated the organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL) The organic phase was concentrated under reduced pressure concentrated again

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

Procedure: Diethyl 3-oxopentanedioate (45.5 ml, 0.25 mol) was added to a suspension of magnesium ethoxide (prepared from magnesium turnings (9 g, 0.375 mol) and iodine (0.1 g) in dry ethanol (275 ml)), and the mixture was heated under reflux for 90 min. 1-Bromo-2-methylpropane (54 ml, 0.5 mol) was added, and the reaction was heated under reflux for 16 h. Further 1-bromo-2-methylpropane (27 ml, 0.25 mol) was added to the boiling mixture, and after 3 h the solvent was evaporated in vacuo. The residue was partitioned between 2 N hydrochloric acid and ether. After extracting the aqueous phase with ether, the combined organics were washed successively with water, 5% sodium bicarbonate, water and brine, then were dried (Na2SO4) and evaporated in vacuo. The residue was distilled to give the title compound as a colourless oil (40 g, 62%), bp 118°-120° C. (1 mmHg). δ (CDCl3): 0.9 (6H, d, J=6Hz), 1.25 (6H, t, J=7Hz), 1.4-1.9 (3H, m), 3.5 (2H, s), 3.7 (1H, d, J=9Hz) and 4.2 (4H, q, J=7Hz). the mixture was heated under reflux for 90 min the reaction was heated under reflux for 16 h after 3 h the solvent was evaporated in vacuo The residue was partitioned between 2 N hydrochloric acid and ether After extracting the aqueous phase with ether the combined organics were washed successively with water, 5% sodium bicarbonate, water and brine were dried (Na2SO4) evaporated in vacuo The residue was distilled

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

Procedure: One gram (5 mmoles) of aluminum ispropoxide was dissolved in 10 ml of Freon TF solvent and 0.7 grams (6 mmoles) of magnesium ethoxide added. After mixing in an ultra-sonic bath, followed by settling of suspended matter, 3 ml of the clear solution was analyzed for Mg and Al. Theory Al: 1.5 mmole, Found Al: 1.5 mmole. Theory Mg: 1.8 mmoles, Found Mg: 0.08 mmoles. Conclusion: Little effect of Aluminum alkoxide on solubility of Magnesium alkoxide in Freon TF, and therefore not a useful system for deacidification of books. added After mixing in an ultra-sonic bath