Phosphorus oxychloride → 7-bromo-4-chloro-6-methoxyquinoline

HRID 1473527Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:13][CH3:14].O=P(Cl)(Cl)[Cl:17]>C(#N)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:17])=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:13][CH3:14]

Participants

Conditions

Temperature: 90 °C

Procedure

To a flask charged with 7-bromo-6-methoxyquinolin-4-ol (0.595 g, 2.342 mmol) was added Acetonitrile (11.71 ml) and POCl3 (0.229 ml, 2.459 mmol) and the resulting suspension heated to 90° C. for 2.5 hr affording a brown solution and near complete conversion to desired product. The mixture was added to a cooled solution of sat. aq. NaHCO3 and extracted with EtOAc (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The organic phase was dried under reduced pressure and purified with an 40 g HP silicycle column ramping EtOAc in heptane (0-50%, 10% DCM throughout) affording isomer separation, both obtained as white solids. NMR indicated that the first eluting peak was the desired isomer, obtained as an off-white solid 7-bromo-4-chloro-6-methoxyquinoline (0.240 g, 0.881 mmol, 37.6% yield). The second peak (looked like about 60:40 ratio of product 1 to 2 by MPLC trace) was not isolated. 1H NMR (400 MHz, CHLOROFORM-d) δ=8.66 (d, J=4.7 Hz, 1H), 8.38 (s, 1H), 7.49 (d, J=4.7 Hz, 1H), 7.47 (s, 1H), 4.08 (s, 3H). m/z (ESI) 272.1 (M+H)+.

Workup

customaffording a brown solution

Sources & evidence

ORD record: ord-594d528c70354f3aa1061e4d3f7beb7d
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012443B2

Reaction notes

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