Boron Trichloride → 2-(2-Fluorophenyl)-5-hydroxy-6-methoxyquinolin-4-one

HRID 38632Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH2:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:21][CH3:22])[C:14]=2[O:19]C)[N:9]=1.B(Cl)(Cl)Cl>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH2:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:21][CH3:22])[C:14]=2[OH:19])[N:9]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 16 (0.2 g, 0.67 mmol) in CH2Cl2 (3 mL) was added 5 mL of BCl3 solution (1 M in CH2Cl2) dropwise at 0°±1° C. The mixture was stirred at 25±1° C. for 2 h and then poured into crushed ice, extracted with EtOAc. The organic layer was washed with H2O, dried over MgSO4 and evaporated. The crude was purified by column chromatography (SiO2, CHCl3: MeOH=15:1) and recrystallized from MeOH to give 37. Yellow solid; yield: 24.1%; mp 268-270° C.; MS (EI, 70 eV): m/z 285 (M+); IR (KBr): 1604.77 (C═O) cm−1; 1H-NMR (DMSO-d6. 200 MHz): δ 3.78 (s, 3H), 6.11 (s, 1H), 7.01 (d, J=7.4 Hz, 1H), 7.36-7.48 (m, 3H), 7.54-7.72 (m, 2H), 12.25 (s, 1H), 14.54 (s, 1H); 13C-NMR (DMSO-d6, 50 MHz): δ 55.80, 106.22, 106.43, 112.88, 116.36 (d, J=23 Hz), 120.81, 121.96 (d, J=13.5 Hz), 125.04, 130.85, 132.67 (d, J=8.6 Hz), 135.09, 141.02, 146.27, 149.29, 158.92 (d, J=247.7 Hz), 181.97; Anal. calcd for C16H12FNO3: C, 67.36; H, 4.24; N, 4.91. Found: C, 67.32; H, 4.26; N, 4.89.

Workup

additionpoured
custominto crushed ice
extractionextracted with EtOAc
washThe organic layer was washed with H2O
dry with materialdried over MgSO4
customevaporated
customThe crude was purified by column chromatography (SiO2, CHCl3: MeOH=15:1)
customrecrystallized from MeOH

Sources & evidence

ORD record: ord-080f8d77e39243f3b660a58d9e2c0690
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524740B2

Reaction notes

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