Electric Literature of 39065-95-7,Some common heterocyclic compound, 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, molecular formula is C7H6ClF2NO, 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.
To a solution of (1R,4R)-9-bromo-4-hydroxy-1-methyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo [1,2-a]pyridine-7-carboxylic acid (49h, 10 mg, 0.031 mmol), 4-[chloro(difluoro)methoxy]aniline (1h, 7.14 mg, 0.037 mmol) in DMF (1 mL) was added HATU (14.03 mg, 0.037 mmol) and DIEA (11.92 mg, 0.092 mmol, 16.07 uL). The mixture was stirred at 15 C. for 5 hr. LCMS showed desired ms was detected. TLC (ethyl acetate_methanol=10:1, Rf=0.40) showed a new spot was formed. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with H2O (10 mL) and extracted with EtAOc (10 mL*3). The combined organic layers were washed with brine, dried over Ns2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, ethyl acetate_methanol=10:1) to give 49i as a white solid. 1H NMR (400 MHz, CDCl3-d) delta 8.09 (d, J=1.3 Hz, 1H), 8.00 (d, J=1.3 Hz, 1H), 7.71 (d, J=8.9 Hz, 2H), 7.25 (s, 1H), 5.46 (br t, J=5.8 Hz, 1H), 5.18 (br s, 1H), 2.76-2.60 (m, 1H), 2.39-2.17 (m, 2H), 1.96-1.86 (m, 1H), 1.53 (d, J=6.6 Hz, 3H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Chlorodifluoromethoxy)aniline, its application will become more common.
Reference:
Patent; Terns, Inc.; ROMERO, F. Anthony; KIRSCHBERG, Thorsten A.; HALCOMB, Randall; XU, Yingzi; (144 pag.)US2020/87283; (2020); A1;,
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