Phosphorus oxychloride → 4-Benzyloxy-2-chloro-7-methoxy-8-methylquinoline

HRID 1516664Notes

Reaction equation

HRID 1516664 reaction equation
O=P(Cl)(Cl)[Cl:3].[CH2:6]([O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[N+:17]([O-])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH2:6]([O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[N:17]=[C:16]([Cl:3])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 576079514-benzyloxy-7-methoxy-8-methylquinoline N-oxide

Product 1

HCID 576079364-Benzyloxy-2-chloro-7-methoxy-8-methylquinolineYield 90.4%

Procedure

POCl3 was added under inert atmosphere at −78° C. to 4-benzyloxy-7-methoxy-8-methylquinoline N-oxide (15, 2.5 g, 8.47 mmol). Then the reaction mixture was allowed to warm up to room temperature, then heated to reflux. After 35 min, the solution was cooled to room temperature and the excess of POCl3 was evaporated under reduced pressure. The residue was partitioned between ice-cooled water and AcOEt, dried (Na2SO4) and evaporated. The residue was triturated in ether, then filtered and successively washed with small portions of methanol and ether to give 2.4 g (90.4%) of the target product 16 as a white powder: m/z=314 (M+H)+.

Workup

  1. temperatureheated to reflux
  2. temperaturethe solution was cooled to room temperature
  3. customthe excess of POCl3 was evaporated under reduced pressure
  4. customThe residue was partitioned between ice-
  5. temperaturecooled water and AcOEt
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customThe residue was triturated in ether
  9. filtrationfiltered
  10. washsuccessively washed with small portions of methanol and ether

Sources & evidence

ORD record
ord-7280515a806f49bb8a47bdf72d1cd9f8
Source dataset
uspto-grants-2012_07
Patent number
US08227407B2

Reaction notes

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