Phosphorus oxychloride → Methyl 4-chloroquinoline-6-carboxylate

HRID 2370778Notes

Reaction equation

HRID 2370778 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N+:11]([O-])=[CH:10][CH:9]=[CH:8]2)=[O:4].P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:8]1[C:7]2[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=2)[N:11]=[CH:10][CH:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 21707072Methyl quinoline-6-carboxylate 1-oxide

Product 1

HCID 58441390Methyl 4-chloroquinoline-6-carboxylateYield 25.8%

Procedure

To 6-(methoxycarbonyl)quinoline-N-oxide from the above step was added phosphoryl trichloride (5 mL, 54.6 mmol). The resulting mixture was then stirred at rt under N2 for 2 h. The reaction was then slowly quenched by addition to an ice cold solution of saturated aqueous NaHCO3 (50 mL) in an ice bath with rapid stirring. The aqueous solution was extracted with EtOAc (3×50 mL). The organic layers were combined, washed with saturated aqueous NaHCO3 (25 mL), H2O (25 mL), dried (MgSO4), and concentrated. Purification by ISCO (40 g SiO2, 0-50% EtOAc/hexanes) gave as the major product, methyl 4-chloroquinoline-6-carboxylate (330 mg, 1.489 mmol, 25.8% yield over 3 steps) (m/z=221.9) as a white solid. Also isolated was the more polar, methyl 2-chloroquinoline-6-carboxylate with same mass (m/z=221.9).

Workup

  1. customThe reaction was then slowly quenched by addition to an ice cold solution of saturated aqueous NaHCO3 (50 mL) in an ice bath with rapid stirring
  2. extractionThe aqueous solution was extracted with EtOAc (3×50 mL)
  3. washwashed with saturated aqueous NaHCO3 (25 mL), H2O (25 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by ISCO (40 g SiO2, 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-002aaf9b66164794adaf9bb45861982a
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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