Yield:676494-55-6 97%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 100; for 4 h;

Steps:

4.1; 5.1; 6.1 Step 1. Synthesis of 3-fluoro-4-(4-formylphenoxy)benzonitrile (C46)

Potassium carbonate (19.9 g, 144 mmol) was added to a mixture of 3,4-difluorobenzonitrile (10.0 g, 71.9 mmol) and 4-hydroxybenzaldehyde (8.78 g, 71.9 mmol) in N,N-dimethylformamide (200 mL). The reaction mixture was heated to 100° C. for 4 hours, whereupon it was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was washed with water (3×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo, affording the product as a yellow solid (17.7 g). By ¹H NMR, this material contained some N,N-dimethylformamide. Yield, corrected for N,N-dimethylformamide: 16.8 g, 69.6 mmol, 97%. ¹H NMR (400 MHz, CDCl₃) δ 9.99 (s, 1H), 7.93 (br d, J=8.6 Hz, 2H), 7.58-7.48 (m, 2H), 7.21 (dd, J=8.4, 8.0 Hz, 1H), 7.14 (br d, J=8.6 Hz, 2H).

References:

US2018/148432,2018,A1 Location in patent:Paragraph 0303; 0304