Phosphorus oxychloride → Ethyl 6-bromo-4-chloroquinoline-3-carboxylate

HRID 1850812Notes

Reaction equation

HRID 1850812 reaction equation
C(O[C:4](=O)[C:5](=[CH:11][NH:12][C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.O=P(Cl)(Cl)[Cl:23]>>[CH2:9]([O:8][C:6]([C:5]1[CH:11]=[N:12][C:13]2[C:14]([C:4]=1[Cl:23])=[CH:15][C:16]([Br:19])=[CH:17][CH:18]=2)=[O:7])[CH3:10]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1591151Diethyl 2-((4-bromophenylamino)methylene)malonate

Product 1

HCID 2764138Ethyl 6-bromo-4-chloroquinoline-3-carboxylateYield 52.2%

Conditions

Temperature
180 °C

Procedure

A 20 mL microwave vial was charged with 2-[(4-bromo-phenylamino)methylene]malonic acid diethyl ester (1.711 g, 5.0 mmol) and POCl3 (phosphoryl chloride, 10.0 mL, 16.8 g, 109 mmol). The vial was capped and the mixture was microwave heated stepwise up to 180° C. (watching the pressure) over 5 min and then kept at 180° C. for 30 min. Excess POCl3 was evaporated and the residue partitioned between CH2Cl2 (40 mL) and 2 N NaOH (aq) (40 mL). The aqueous layer was extracted with CH2Cl2 (2×40 mL). The organic layers were combined, dried with Na2CO3 and evaporated. The residue was purified on column (silica gel, CH2Cl2 as eluent). Pure fractions were pooled, evaporated and the residue dried under vacuum to give 0.821 g (52%) of 6-bromo-4-chloroquinoline-3-carboxylic acid ethyl ester. MS (ESI+) m/z 314, 316 (MH+).

Workup

  1. customThe vial was capped
  2. customover 5 min
  3. customExcess POCl3 was evaporated
  4. customthe residue partitioned between CH2Cl2 (40 mL) and 2 N NaOH (aq) (40 mL)
  5. extractionThe aqueous layer was extracted with CH2Cl2 (2×40 mL)
  6. dry with materialdried with Na2CO3
  7. customevaporated
  8. customThe residue was purified on column (silica gel, CH2Cl2 as eluent)
  9. customevaporated
  10. customthe residue dried under vacuum

Sources & evidence

ORD record
ord-33bc0e6da21641eebdd59782a6a2ebaa
Source dataset
uspto-grants-2015_02
Patent number
US08957092B2

Reaction notes

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