Triethylamine → 8-Chloro-2-(pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester

HRID 572120Notes

Reaction equation

HRID 572120 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([CH:7](O)[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[CH2:6])[CH3:2].[Cl:16][C:17]1[C:22]([NH2:23])=[C:21](I)[CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:5]1[CH2:6][C:21]2[C:22](=[C:17]([Cl:16])[CH:18]=[CH:19][CH:20]=2)[NH:23][C:7]=1[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[O:15])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 132189252-Chloro-6-iodoanilineHCID 15812391Ethyl-2-(hydroxy(pyridin-3-yl)methyl)acrylate

Product 1

HCID 666919028-Chloro-2-(pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylic acid ethyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A degassed mixture of 2-[(hydroxy)(pyridin-3-yl)methyl]acrylic acid ethyl ester (8.2 g, 39.6 mmol), 6-chloro-2-iodoaniline (10.0 g, 39.5 mmol), triethylamine (9 mL, 122 mmol) and palladium(II) acetate (300 mg) in acetonitrile (80 mL) was heated at 70° C. overnight. The mixture was cooled to room temperature and partitioned between ethyl acetate (200 mL) and water (100 mL). The aqueous layer was separated and the organic layer was washed with brine (50 mL), filtered, dried (phase separator) and concentrated in vacuo to give a crude solid. This was washed with a minimum of ice-cold diethyl ether to yield 8-chloro-2-(pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (10.8 g, 87%) as a white solid. δH (CDCl3) 8.73 (m, 2H), 8.04 (m, 1H), 7.66 (dd, J 7.9, 5.5 Hz, 1H), 7.18 (m, 1H), 7.05 (m, 1H), 6.94 (m, 1H), 6.29 (s, 1H), 3.99 (m, 4H), 1.04 (t, J 7.1 Hz, 3H). LCMS (ES+) 315.0 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (200 mL) and water (100 mL)
  3. customThe aqueous layer was separated
  4. washthe organic layer was washed with brine (50 mL)
  5. filtrationfiltered
  6. customdried (phase separator)
  7. concentrationconcentrated in vacuo
  8. customto give a crude solid
  9. washThis was washed with a minimum of ice-cold diethyl ether

Sources & evidence

ORD record
ord-980a07723755405a8843db84202ab62d
Source dataset
uspto-grants-2015_05
Patent number
US09029392B2

Reaction notes

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