Main applications of 4-(4-fluorophenoxy)benzaldehyde_Kain Industrial Additives

Background and overview^[1]

4-(4-Fluorophenoxy)benzaldehyde can be used as a pharmaceutical synthesis intermediate. If 4-(4-fluorophenoxy)benzaldehyde is inhaled, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell. ; If eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[1]

4-(4-Fluorophenoxy)benzaldehyde was prepared as follows: To a solution of 4-fluorobenzaldehyde (2.48g, 20mmol) and 4-fluorophenol (2.46g, 22mmol) in DMF (50mL) was added Potassium carbonate (5.52g, 40mmol). The mixture was stirred at 110°C for 16 hours. After the reaction, it was poured into water and extracted with ethyl acetate (80 mL × 3). The combined organic layers were washed with water (100 mL × 3) and saturated brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel chromatography (petroleum ether: EtOAc = 10:1) to obtain 4-(4-fluorophenoxy)benzaldehyde (3.25 g, yield 75%).

Apply^[1]

4-(4-Fluorophenoxy)benzaldehyde can be used as a pharmaceutical synthesis intermediate. For example, prepare the following compounds:

To N-[(2S,3R)-5-[(1S)-2-hydroxy-1-methyl-ethyl]-3-methyl-2-(methylaminomethyl)-6-oxo Mixture of 3,4-dihydro-2H-1,5-benzoxazin-10-yl]-2-[4-(trifluoromethyl)phenyl]acetamide (64.00 mg, 139.58 μmol, 1.00 equiv) and 4-(4-fluorophenoxy)benzaldehyde (36.71 mg, 139.588 μmol) in MeOH/DCE (1 mL/0.5 mL) was added with 1.00 equiv of AcOH (1 drop). After 2 hours, NaBH3CN (17.54mg, 279.16μmol, 2.00Eq) was added in one go. Then heat to 45°C for 16 hours. TLC showed the reaction was complete. The mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC to give the title compound (21.35 mg, 28.35 μmol, 20% yield) as a white solid. 1HNMR (400MHz, DMSO-d6) δ8.73 (s, 1H), 7.89 (d, J = 7.5Hz, 1H), 7.66 (d, J = 7.9Hz, 2H), 7.54 (d, J = 7.9Hz, 2H),7.28-7.14(m,4H),7.10(d,J＝7.5Hz,1H),7.00(dd,J＝4.6,9.0Hz,2H),6.91-6.75(m,3H),4.83(t ,J＝5.3Hz,1H),4.61(br.s.,1H),4.51-4.35(m,1H),4.00-3.76(m,2H),3.67-3.44(m,3H),3.29-3.17( m,2H),2.96-2.79(m,1H),2.14-1.87(m,4H),1.08(d,J＝6.6Hz,3H),0.67(d,J＝6.2Hz,3H).ESI[M +H]＝694.2.

Main reference materials

[1] (WO2016019588) OXACAZONE COMPOUNDS TO TREAT CLOSTRIDIUM DIFFICILE