Electric Literature of 399-94-0, These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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.
Method B:To a solution of 1-bromo-2,5-difluorobenzene (42.2 g, 0.218 mol) in toluene (85 mL) at -10 to -5 C. was added iPrMgCl/LiCl solution (1.0 M in THF, 240 mL, 0.24 mol) dropwise over 1.5 h. The reaction solution was then aged for 30 min at -10 to -5 C.In a separate vessel, Weinreb amide 4 (28 g, 0.109 mol) was dissolved in THF (112 mL), cooled to 15 C. and then charged to the above Grignard solution over about 30 min, while the internal temperature was maintained at -10 to -5 C. The reaction mixture was then warmed to 20 C. over 1 h, and aged for additional 1 h at 20 C. for complete reaction. The reaction mixture was quenched with an aqueous HCl solution (32.5 g of concentrated hydrochloric acid in 110 mL of water) at 0 to 10 C. over 30 min. The organic phase was washed with 10% NaCl solution (200 mL×2). The organic phase was solvent switched to iPrOH (final volume about 270 mL) and water (380 mL) was added over 1 h at 20 C. Solids were filtered and washed with 40% iPrOH in water (60 mL×2). The wet cake was dried under vacuum at 45 C.1H-NMR (500 MHz, CDCl3): delta 7.56 (m, 1H), 7.25 (m, 1H); 7.15 (m, 1H), 5.67 (d, J=7.3 Hz, 1H), 5.24 (m, 1H), 2.91 (m, 1H), 2.68 (m, 1H), 2.00 (t, J=2.43, 1H), 1.45 (s, 9H). 13C-NMR (125 MHz, CDCl3): delta 159.03 (dd, J=245.5, 1.8 Hz), 157.4 (d, J=248.0 Hz), 124.6 (dd, J=15.4, 6.2 Hz), 122.2 (dd, J=24.6, 9.8 Hz), 118.4 (dd, J=27.1, 8.0 Hz), 117.6 (DD, J=25.2, 3.7 Hz), 80.4, 78.4, 72.1, 57.9 (d, J=7.5 Hz), 28.5, 22.3.
The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Xu, Feng; Kim, Mary M.; Kohmura, Yoshinori; Sladicka, Tricia; Rosen, Jonathan D.; Zacuto, Michael J.; US2009/187028; (2009); A1;,
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