Extended knowledge of 366-99-4

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference of 366-99-4,Some common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, molecular formula is C7H8FNO, 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.

Cyanuric chloride (11. 07g, 60 mmol) was dissolved in 40 mL CH3CN and was cooled toabout-20 C. To this was added DIEA (11.5mL, 60 mmol) followed by3-fluoro-4-methoxyaninline (8.47g, 60 mmol) in 20 mLCH3CN (reaction froze). The reaction was allowed to warm to room temperature after about1 hour at-20 C. TLC (2percent CH3OH/CH2Cl2) and mass spectroscopy indicated the presence of the compound 124. The reaction mixture was cooled to about 0 c before adding DIEA (11.5 mL, 66mmol).2-Aminomethyl-l-ethylpyrrolidine (7.77 g, 60 mmol) in CH3CN (10 mL) was added. The reaction was allowed to warm to rt and stirred overnight. Then DIEA (11.5 mL, 66 mmol) andS- (+)-2-methoxyethylpyrrolidine (6.91 g, 60 mmol) in 20mL 1,4-dioxane were added. The reaction was heated at about50 C overnight. The solvent was removed in vacuo, and the resulting residue was purified by flash chromatography on silica gel packed in ethyl acetate. The front running impurities were removed and subsequently the eluent was increased in polarity to 10percent CH30H: ethyl acetate. The material collected from the column was then dissolved in water and extracted inCH2C12 (4 times), dried overMgSO4, and concentrated to dryness to give a brown solid145 (9.7 g, 27.6percent yield),71-72 C ; HPLC: Inertsil ODS-3V C18, 40: 30: 30[KH2PO4 (O.O1M, pH 3.2) :CH30H : CH3CN], 264nm, Rt 5.37 min, 90.3 percent purity ; 1H NMR (600 MHz, CDC13,55 C) No. 7.69 (s, 1H), 7.08 (d, J= 7.8 Hz, 1H), 6.86 (t, J = 9 Hz, 1H), 4.29 (s, 1H), 3.90-3. 96 (m, 1H), 3.84 (s, 3H), 3.63-3. 81 (m,6H), 3.35 (s, 3H), 3.23-3. 25 (m, 1H), 2. 85(broad s, 1H), 2.78 (broad s 1H), 2.14 (broad s, 2H), 1.89-2. 04 (m, 6H), 1.37 (apparent t, J= 7.2 Hz, 3H) ; 13C NMR(150. 8 MHz, CDC13, 55 C)8 165. 8, 163.8 (2C), 152.3 (d,Jc-f= 243.5 Hz), 143.0 (142.9, rotamer or diastereumer), 133.7 (133.67, rotamer or diastereomer), 115.0, 114.4, 109.1 (108. 9, rotamer or diastereomer), 72.8, 66.6, 59.0,. 57. 0,56. 6,53. 7,51. 0,46. 8, 42.2, 28.4 (28. 2, rotamer or diastereomer), 23.1(23. 0, rotamer or diastereomer), 10.9 ; MS (ESI)inlz 460.2 (M+H, 44.7), 251.1 (47.7), 235.1 (27.5), 231.1 (37.4), 230.6 (100), 214.6 (36.5).

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; REDDY US THERAPEUTICS, INC.; WO2004/26844; (2004); A1;,
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