96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2 Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione Ethyl difluoroacetate (4.06 g, 32.7 mmol) was dissolved in methyl tert-butyl ether (50 mL). To the stirred solution was added 25 weight % sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected and washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C. |
96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2 Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione, Ethyl difluoroacetate (4.06 g, 32.7 mmol) was placed in a 250 mL Erlenmeyer flask, and dissolved in methyl t-butyl ether (50 mL). To the stirred solution was added 25 weight % sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected and washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C.; 1 H NMR (D6 -DMSO) 8.0 (m, 3H), 7.3 (t, 1H), 6.9 (s, 1H), 6.5 (t, 1H), 3.9 (s, 3H). |
96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2 Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione Ethyl difluoroacetate (4.06 g, 32.7 mmol) was dissolved in methyl t-butyl ether (50 mL). To the stirred solution was added 25 weight % sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected and washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C. |
96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2 Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione Ethyl difluoroacetate (4.06 g, 32.7 mmol) was placed in a 250 mL Erlenmeyer flask, and dissolved in methyl tert-butyl ether (50 mL). To the stirred solution was added 25% sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> from Step 1 (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected, washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C.; 1 H NMR (DMSO-d6) 8.0 (m, 3H), 7.3 (t, 1H), 6.9 (s, 1H), 6.5 (t, 1H), 3.9 (s, 3H). |
96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2: Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione Ethyl difluoroacetate (4.06 g, 32.7 mmol) was placed in a 250 mL Erlenmeyer flask, and dissolved in methyl tert-butyl ether (50 mL). To the stirred solution was added 25% sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> from Step 1 (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected, washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C.; 1 H NMR (DMSO-d6) 8.0 (m, 3H), 7.3 (t, 1H), 6.9 (s, 1H), 6.5 (t, 1H), 3.9 (s, 3H). |
96% |
With hydrogenchloride; sodium methylate; In tert-butyl methyl ether; |
Step 2: Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione. Ethyl difluoroacetate (4.06 g, 32.7 mmol) was dissolved in methyl tert-butyl ether (50 mL). To the stirred solution was added 25 weight % sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> from Step 1 (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected and washed with water (2*50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C. |
96% |
With sodium methylate; In tert-butyl methyl ether; for 16h; |
Step 2: Preparation of 4,4-difluoro-1-(3-fluoro-4-methoxyohenyl)-butane-1,3-dione. ethyl difluoroacetate (4.06 g, 32.7 mmol) was dissolved in methyl t-butyl ether (50 ML).. To the stirred solution was added 25 weight % sodium methoxide (7.07 g, 32.7 mmol) followed by <strong>[455-91-4]3'-fluoro-4'-methoxyacetophenone</strong> (5.0 g, 29.7 mmol).. After stirring for 16 hours, 1N HCl (50 ML) was added.. The organic layer was collected and washed with water (2*50 ML), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70-72 C. |
94.2% |
With sodium methylate; In dichloromethane; for 48h; |
1.79 g (14.4 mmol) of ethyl difluoroacetate was added to a 50 ml round-bottomed flask, dissolved with 25 ml of methylene chloride, 2.2 g (13.1 mmol) of <strong>[455-91-4]3-fluoro-4-methoxyacetophenone</strong> and 98% of it were added Sodium methoxide 0.79 g (14.4 mmol). After stirring for 36 hours, 5 ml of 1N hydrochloric acid was added, and the organic phase was washed with water (2 x 15 ml), dried over anhydrous magnesium sulfate, suction filtered, and petroleum ether was added to precipitate a tan product.Yield 93.1%. |