These common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: ethers-buliding-blocks
To a stirred light brown solution of 10.0 g (49.6 mmol) 3-Fluoro-4-methoxy aniline in 56 ml DCM was added rapidly a solution of 4.38 g (52 mmol, 1.05 eq.) NaHCO3 in 70 ml of water. To the resulting biphasic mixture was added under vigorous stirring 5.72 ml (74.4 mmol, 1.5 eq.) methyl chloroformate over a period of 30 min. The light brown reaction mixture was stirred for 1.5h at RT. The organic phase was separated and washed twice with a total amount of 50 ml water, and the combined aqueous phases were washed twice with a total amount of 100 ml DCM. The combined organic phases were dried over 2 g Na2SO4 and filtered with suction on a funnel with a fritted disk. The cake was washed in total with 50 ml DCM. The DCM was partially removed under reduced pressure to about 1/3 of its original volume and then 70 ml heptane was added dropwise under stirring within 30 min, whereby the product precipitated. From this suspension, DCM was completely removed under reduced pressure. Finally, the suspension was stirred in an ice bath for 1h, the crystals were filtered off with suction on a funnel with a fritted disk and washed with three 10 ml portions, in total with 30 ml ice cold heptane. The wet off-white crystals were dried at 50°C in vacuo to yield 9.65 g (97.7percent of theory) of the title compound as off-white crystals (m.p. = 96.1-96.5°C) 1H-NMR data (CDCl3, 300 MHz): delta 7.29 (m, 1H), 6.98 (m, 1H,), 6.89 (dd, 1H), 6.44 (br s, 1H), 3.86 (s, 3H), 3.77 (s, 3H). MS m/e (percent): 200 ([M+H]+, 100).
The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F. Hoffmann-La Roche AG; EP2011783; (2009); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem