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

HRID 1850815Notes

Reaction equation

HRID 1850815 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 50%

Procedure

2-[(4-Bromophenylamino)methylene]malonic acid diethyl ester (5 g) was heated with POCl3 (phosphoryl chloride, 31.5 mL) at 150° C. in a sealed tube for about 6 h. The excess POCl3 was removed by rotavapor and the crude mixture was diluted with dichloromethane. The dichloromethane extract was washed with 10% NaOH solution, dried over sodium sulphate and purified by column chromatography (Silica gel, hexane/ethyl acetate 80:20) to give 2.3 g (50%) of 6-bromo-4-chloroquinoline-3-carboxylic acid ethyl ester. 1H NMR (300 MHz, CDCl3) δ 9.22 (s, 1H, aromatic), 8.60 (d, 1H, J=2.1 Hz, aromatic), 8.04 (d, 1H, J=9 Hz, aromatic), 7.95-7.85 (m, 1H, aromatic), 4.53 (q, 2H, J=7 Hz, —CH2—), 1.50 (t, 3H, J=7 Hz, —CH3); LC-MS (m/z) 315.8 (M+1).

Workup

  1. customThe excess POCl3 was removed by rotavapor
  2. additionthe crude mixture was diluted with dichloromethane
  3. extractionThe dichloromethane extract
  4. washwas washed with 10% NaOH solution
  5. dry with materialdried over sodium sulphate
  6. custompurified by column chromatography (Silica gel, hexane/ethyl acetate 80:20)

Sources & evidence

ORD record
ord-4ccff49e70084029aa09a93be9fdfb89
Source dataset
uspto-grants-2015_02
Patent number
US08957092B2

Reaction notes

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