366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 366-99-4
To a stirred suspension of 3-fluoro-p-anisidine (3.00 g, 21 mmol) in CH2Cl2 (10 mL) is added acetic anhydride (2.0 mL, 21 mmol) over 1 h while maintaining the temperature between 25-30¡ã C. using a cold water bath. The solution is then stirred for 2 h at 25¡ã C. Additional 1 mL of acetic anhydride is added to the solution, which is then stirred for an additional 2 h. Hexane (30 mL) is slowly added to the mixture over 1 h. The product is collected by filtration, concentrated in vacuo and dried in oven to give 3.40 g (90percent yield) of N-(3-fluoro-4-methoxyphenyl)acetamide as tan crystals. 1H NMR (400 MHz, CDCl3) delta 7.41, 7.19, 7.11, 6.90, 3.87, 2.16. In a 100 mL, three-necked flask equipped with a thermometer and a dropping funnel chilled in an ice-salt bath, N-(3-fluoro-4-methoxyphenyl)acetamide (3.0 g, 16 mmol) is dissolved in 98percent sulfuric acid, care being taken that the temperature does not rise above 5¡ã C. To this solution 2.6 mL of nitric acid is added dropwise at such a rate that the temperature does not rise above 5¡ã C. After all the nitric acid is added, the viscous orange mass is poured onto 50 g of cracked ice and the mixture is thoroughly stirred. The yellow crystals that separate are filtered off and thoroughly washed with water to yield 3.33 g (89percent yield) of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide as yellow crystals. 1H NMR (400 MHz, DMSO-d6) delta 10.60, 10.17, 7.75, 7.73, 7.62, 7.59, 4.03, 3.92, 2.06. A suspension of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide (3.0 g, 13 mmol) in 38 mL of water, 38 mL of HCl and 15 mL of ethanol is refluxed for 30 minutes. On cooling, crystals that separate are recrystallized from ethanol to yield 0.71 g (29percent yield) of 5-fluoro-4-methoxy-2-nitroaniline as red crystals. 1H NMR (400 MHz, CDCl3) delta 7.68, 6.56, 6.04, 3.87. Example 603 is obtained according to Method F, making non-critical modifications. Yield 60percent. HRMS (ESI) calcd for C12H11FN4O5+H 311.0792 found 311.0798.
Statistics shows that 366-99-4 is playing an increasingly important role. we look forward to future research findings about 3-Fluoro-4-methoxyaniline.
Reference:
Patent; Piotrowski, David W.; Rogers, Bruce N.; McWhorter JR., William W.; Walker, Daniel Patrick; Corbett, Jeffrey W.; Groppi JR., Vincent E.; Rudmann, Daniel G.; US2003/236287; (2003); A1;,
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