Phosphorus oxychloride → 7-Bromo-4-chloro-6-methylquinoline

HRID 1473523Notes

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[CH3:13].O=P(Cl)(Cl)[Cl:16]>C(#N)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:16])=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH3:13]

Participants

Conditions

Temperature: 90 °C

Procedure

To a flask charged with 7-bromo-6-methylquinolin-4-ol (0.675 g, 2.84 mmol) was added acetonitrile (14.18 ml) and POCl3 (0.277 ml, 2.98 mmol) and the resulting suspension was heated to 90° C. for 2.5 h affording a brown solution and near complete conversion to desired product. The material was added to cold sat. aq. NaHCO3 and extracted with EtOAc (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure and purified with an 40 g Silicycle HP column ramping EtOAc in heptane (0-50%, 10% DCM throughout) affording isomer separation, both obtained as off-white solids. The first eluting isomer corresponds to product based on the proton NMR, obtained as a light yellow solid, 7-bromo-4-chloro-6-methylquinoline (240 mg, 0.936 mmol, 33.0% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.68 (d, J=4.70 Hz, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.43 (d, J=4.69 Hz, 1H), 2.59 (s, 3H). m/z (ESI) 256.1/258.1 (M+H)+.

Workup

customaffording a brown solution

Sources & evidence

ORD record: ord-e79aeb3f57234cc7b3f9d2ccf6887633
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012443B2

Reaction notes

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