Phosphorus oxychloride → HCID 86687536, compound

HRID 1473484Notes

Reaction equation

HRID 1473484 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[CH:7][CH:8]=[N:9]2)=[C:4]([CH3:13])[CH:3]=1.BrC1C=C(C)C=C2C=1C(O)=CC=N2.O=P(Cl)(Cl)[Cl:29]>C(#N)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:29])=[CH:7][CH:8]=[N:9]2)=[C:4]([CH3:13])[CH:3]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 178422416HCID 178422416, compoundHCID 178422429HCID 178422429, compound

Product 1

HCID 86687536HCID 86687536, compoundYield 49.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a vial charged with a mixture of 7-bromo-5-methylquinolin-4-ol and 5-bromo-7-methylquinolin-4-ol (0.09 g, 0.378 mmol) was added acetonitrile (1.890 ml) followed by the addition of POCl3 (0.035 ml, 0.378 mmol). The mixture was heated to 90° C. for 1.5 hr. The mixture was dried under reduced pressure and the crude residue purified with a 25 g Interchim HP spherical silica column (15 μm spherical) (0 to 50%, 10% DCM throughout) providing adequate separation of regioisomers. The major, first eluting isomer was isolated cleanly to yield 7-bromo-4-chloro-5-methylquinoline (48 mg, 0.187 mmol, 49.5% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.02 (s, 4H) 7.46 (d, J=4.69 Hz, 1H) 7.50 (dd, J=2.01, 0.93 Hz, 1H) 8.15-8.19 (m, 1H) 8.67 (d, J=4.70 Hz, 1H). m/z (ESI) 256.1 (M+H)+.

Workup

  1. customThe mixture was dried under reduced pressure
  2. customthe crude residue purified with a 25 g Interchim HP spherical silica column (15 μm spherical) (0 to 50%, 10% DCM throughout)
  3. customproviding adequate
  4. customseparation of regioisomers
  5. customThe major, first eluting isomer was isolated cleanly

Sources & evidence

ORD record
ord-26dd2f59e50e4ac6bf435699a5b6d6d8
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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