Potassium Carbonate → Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

HRID 393325Notes

Reaction equation

HRID 393325 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1[CH:4]=O.C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]([F:27])([F:26])/[CH:19]=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CN(C)C=O>[Cl:10][C:7]1[CH:6]=[C:3]2[C:2](=[CH:9][CH:8]=1)[NH:1][CH:19]([C:18]([F:17])([F:27])[F:26])[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:4]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27738982-Amino-5-chlorobenzaldehydeHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate

Product 1

HCID 21883646Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The 2-amino-5-chlorobenzaldehyde from Step 1 (15.0 g, 96 mmol), anhydrous potassium carbonate (27.6 g, 200 mmol), and ethyl 4,4,4-trifluorocrotonate (34 mL, 200 mmol) were mixed in anhydrous dimethyformamide (60 mL) and heated at 100° C. for 7 hours. The contents were allowed to cool and partitioned between ethyl acetate (200 mL) and water (200 mL). The aqueous layer was extracted with ethyl acetate (1×100 mL). The ethyl acetate extracts were combined and washed with brine (1×200 mL), dried over MgSO4, and concentrated in vacuo leaving a dark oil which solidified upon standing. The solid was purified by flash chromatography (silica gel; ethyl acetate-hexanes, 1:9). Fractions containing the desired product were combined, concentrated in vacuo and the residue recrystallized from ethyl acetate-hexanes to afford the ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate as a yellow solid (16.36 g, 56%): mp 132.6-134.2° C. 1H NMR (CDCl, 300 MHz) 7.61 (s, 1H), 7.10 (m, 2H), 6.55 (d, 1H, J=8.0 Hz), 5.10 (q, 1H, J=6.0 Hz), 4.55 (brs, 1H), 4.23 (m, 2H), 1.32 (t, 3H, J=7.0 Hz). FABHRMS m/z 306.0468 (M+H+, Calc'd 306.0509). Anal. Calc'd for C13H11NO2F3Cl: C, 51.08; H, 3.63; N, 4.58. Found: C, 50.81; H, 3.49; N, 4.72.

Workup

  1. temperatureto cool
  2. custompartitioned between ethyl acetate (200 mL) and water (200 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (1×100 mL)
  4. washwashed with brine (1×200 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customleaving a dark oil which
  8. customThe solid was purified by flash chromatography (silica gel; ethyl acetate-hexanes, 1:9)
  9. additionFractions containing the desired product
  10. concentrationconcentrated in vacuo
  11. customthe residue recrystallized from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-19472b4de8ba43b8b60c9b57072b5574
Source dataset
uspto-grants-2004_10
Patent number
US06806288B1

Reaction notes

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