3-Fluoro-4-phenoxy-benzaldehyde synthesis

Yield: 52%

Reaction Conditions:

with caesium carbonate in N,N-dimethyl-formamide at 120; for 0.5 h;

Steps:

59.1 Step-1: Synthesis of 4-(p-tolyloxy)benzaldehyde
To a stirred solution of 3,4-difluorobenzaldehyde (0.5 g, 5.31 mmol, 1.0 eq.), Phenol (0.95 g, 6.3 mmol, 1.2 eq.) in DMF (15 mL) was added Cs₂CO₃ (3.46 g, 10.6 mmol, 2.0 eq.) at RT. The reaction mixture was stirred at same temperature for 30 min and heated at 120° C. for 16 h. Following this, reaction was allowed to cool to RT and added water (50 mL) extracted using ethyl acetate (3×10 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na₂SO₄, filtered and concentrated under vacuum to get the solid residue which was purified by was purified by normal phase silica-gel column chromatography to get the title compound as yellow solid (0.6 g, 52%). LCMS: 216.9 [M+1]⁺

References:

INTEGRAL BIOSCIENCES PRIVATE LIMITED;CHAKRAVARTY, Sarvajit;PENDHARKAR, Dhananjay;RAMACHANDRAN, Sreekanth A.;BATHULA, Chandramohan;SONI, Sanjeev;KUMAR, Vivek;SAEED, Uzma;DANODIA, Abhinandan Kumar;SHARMA, Ankesh;JADHAVAR, Pradeep S. US2020/206233, 2020, A1 Location in patent:Paragraph 0485-0486