Application of 450-91-9, These common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-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.
To a solution of EDCI?HCl (573.2 mg, 2.99 mmol) in DMF (7 mL) and CH2Cl2 (7 mL) were successively added OxymaPure® (425.0 mg, 2.99 mmol) and S1 (1.00 g, 2.72 mmol) at room temperature. After stirring the reaction mixture for 5 min, 4-fluoro-2-methoxyaniline (470.6 mg, 2.99 mmol) dissolved in DMF (1 mL) and DIPEA (590 muL, 4.08 mmol) were added, the reaction mixture was stirred at the same temperature for 11 h. The volatiles were removed under reduced pressure. The residue was diluted with ethyl acetate and 1 N HCl aq. was added. The resulting mixture was extracted with ethyl acetate twice, the combined organic layers were washed with aqueous saturated NaHCO3 twice, H2O, brine and dried over Na2SO4. After filtration, the residue was concentrated under reduced pressure and dried in vacuo to give crude amide as brown solid. To the amide in DMF (9 mL) was added piperidine (240 muL, 4.08 mmol) and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate and H2O was added. The resulting mixture was extracted with ethyl acetate twice, the combined organic layers were washed with H2O, brine, dried over Na2SO4. Filtrate was concentrated and the resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane = 12/88 to 100/0) to give S2 (464.9 mg, 1.73 mmol, 64percent over 2 steps) as a pale brown oil.Pale brown oil; [alpha]D27 ?6.1 (c 0.44, CH3OH); 1H NMR (400 MHz, CD3OD) delta 8.01 (dd, J = 8.8 , 6.2 Hz, 1H), 6.84 (dd, J = 10.5, 2.7 Hz, 1H), 6.66 (ddd, J = 8.8, 8.6, 2.7 Hz, 1H), 3.89 (s, 3H), 3.46 (dd, J = 7.3, 5.6 Hz, 1H), 1.86?1.77 (m, 1H), 1.66?1.53 (m, 2H), 1.35?1.29 (m, 2H), 0.93 (d, J = 6.6 Hz, 3H), 0.92 (d, J = 6.6 Hz, 3H); 13C NMR (100 MHz, CD3OD) delta 176.3, 161.4 (d, J = 240.6 Hz), 152.7 (d, J = 10.2 Hz), 124.3 (d, J = 3.6 Hz), 123.4 (d, J = 9.5 Hz), 107.1 (d, J = 21.9 Hz), 100.2 (d, J = 27.0 Hz), 56.9, 56.6, 35.8, 34.2, 29.2, 23.0, 22.9; 19F NMR (376 MHz, CD3OD) delta ?117.4; IR (neat) nu 3019, 2959, 1673, 1611, 1531, 1465, 1415, 1216, 757, 669 cm?1; HRMS (ESI) calcd. for C14H22N2O2F m/z 269.1660 [M+H]+, found 269.1651.
The synthetic route of 450-91-9 has been constantly updated, and we look forward to future research findings.
Reference:
Article; Nonoyama, Akihito; Kumagai, Naoya; Shibasaki, Masakatsu; Tetrahedron; vol. 73; 11; (2017); p. 1517 – 1521;,
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