4-Fluoroaniline → Ethyl 6-bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1048872Notes

Reaction equation

HRID 1048872 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:7]=1.CO[CH:19](OC)[N:20]([CH3:22])C.[F:25][C:26]1[CH:32]=[CH:31]C(N)=[CH:28][CH:27]=1>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:20]([C:19]1[CH:31]=[CH:32][C:26]([F:25])=[CH:27][CH:28]=1)[CH:22]=[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:8]2=[O:15]

Participants

6

Reactant 3

HCID 97314-FluoroanilineHCID 78373Dimethylformamide dimethyl acetalHCID 45790368Ethyl 3-(5-bromo-2-fluorophenyl)-3-oxopropanoate

Product 1

HCID 121447944Ethyl 6-bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Compound C (2.87 g, 9.93 mmol, 1.00 eq) and N,N-dimethylformamide dimethyl acetal (1.87 mL, 14.9 mmol, 1.50 eq) were dissolved in DMF (33 mL) in a microwave vial and heated in a microwave reactor at 120° C. for 15 minutes. To this mixture was then added 4-fluoroaniline (1.41 mL, 14.9 mmol, 1.50 eq) and the reaction was heated in a microwave reactor at 150° C. for 20 minutes. The reaction mixture was diluted with ethyl acetate and washed with water (2×). The aqueous layers were back-extracted with ethyl acetate and the combined organics were dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using 0-45% hexanes/ethyl acetate afforded 3.79 g (98%) of the title compound as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.31 (d, J=2.4 Hz, 1H), 7.81 (dd, J=9.1, 2.4 Hz, 1H), 7.77-7.73 (m, 2H), 7.54-7.50 (m, 2H), 6.92 (d, J=9.0 Hz, 1H), 4.20 (q, J=7.1 Hz, 2H), 1.25 (t, J=7.1 Hz, 3H); ES-MS [M+1]+: 390.2.

Workup

  1. washwashed with water (2×)
  2. extractionThe aqueous layers were back-extracted with ethyl acetate
  3. dry with materialthe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica gel using 0-45% hexanes/ethyl acetate

Sources & evidence

ORD record
ord-d5b813d4ec864e228156f840ac0d92e7
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

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