Phosphorus oxychloride → 4-Chloro-7-methoxy-2-phenylquinoline

HRID 1815693Notes

Reaction equation

HRID 1815693 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:3]=1.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487676HCID 178487676, compound

Product 1

HCID 107544774-Chloro-7-methoxy-2-phenylquinoline

Procedure

The product of Step 1a (21.7 g, 86.4 mmole) was suspended in POCl3 (240 mL). The suspension was refluxed for 2 hours. After removal of the POCl3 in vacuo, the residue was partitioned between EtOAc (IL), and cold aqueous NaOH (generated from 1.0N 200 mL NaOH and 20 mL 10.0 N NaOH) and stirred for 15 min. The organic layer was washed with water (2×200 mL), brine (200 mL), dried (MgSO4), and concentrated in vacuo to supply 4-chloro-2-phenyl-7-methoxyquinoline (21.0 g, 90%) as a light brown solid. 1H NMR (DMSO-d6) δ: 3.97 (s, 3H), 7.36 (dd, J=9.2, 2.6 Hz, 1H), 7.49-7.59 (m, 4H), 8.08 (d, J=9.2 Hz, 1H), 8.19 (s, 1H), 8.26-8.30 (m, 2H); 13C NMR (DMSO-d6) δ: 55.72, 108.00, 116.51, 119.52, 120.48, 124.74, 127.26, 128.81, 130.00, 137.58, 141.98, 150.20, 156.65, 161.30. LC-MS (retention time: 1.547, Method D), MS m/z 270 (M++1).

Workup

  1. temperatureThe suspension was refluxed for 2 hours
  2. customAfter removal of the POCl3 in vacuo
  3. customthe residue was partitioned between EtOAc (IL), and cold aqueous NaOH (generated from 1.0N 200 mL NaOH and 20 mL 10.0 N NaOH)
  4. washThe organic layer was washed with water (2×200 mL), brine (200 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo to supply 4-chloro-2-phenyl-7-methoxyquinoline (21.0 g, 90%) as a light brown solid

Sources & evidence

ORD record
ord-a01e5a84fc6b4569a8a0c17a3da99576
Source dataset
uspto-grants-2005_04
Patent number
US06878722B2

Reaction notes

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