Ethyl pyruvate → Ethyl 6-bromo-7-fluoroquinoline-2-carboxylate

HRID 2423498Notes

Reaction equation

HRID 2423498 reaction equation
[Br:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([N+:10]([O-])=O)=[C:6]([CH:9]=1)[CH:7]=O.[C:14]([O:19][CH2:20][CH3:21])(=[O:18])[C:15]([CH3:17])=O.[Sn](Cl)Cl>C(O)C.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:9]=[C:6]2[C:5](=[CH:4][C:3]=1[F:13])[N:10]=[C:15]([C:14]([O:19][CH2:20][CH3:21])=[O:18])[CH:17]=[CH:7]2

Participants

6

Reactant 3

HCID 12041Ethyl pyruvateHCID 24479Stannous ChlorideHCID 113796385-Bromo-4-fluoro-2-nitrobenzaldehyde

Product 1

HCID 53404702Ethyl 6-bromo-7-fluoroquinoline-2-carboxylateYield 20.4%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
70 °C

Procedure

5-Bromo-4-fluoro-2-nitro-benzaldehyde (1.50 g, 6.05 mmol) and ethyl pyruvate (737.4 mg, 6.35 mmol) in ethanol (15 mL) was added via canula to zinc(II)chloride (4.12 g, 30.24 mmol), tin(II)chloride (5.73 g, 30.24 mmol), and activated 4 Å molecular sieve pellets (1.50 g) in ethanol (15 mL) under argon. The mixture was heated at 70° C. in an oil bath for four hours, then allowed to cool to room temperature, and carefully quenched with saturated sodium bicarbonate. Ethyl acetate was added and the mixture was filtered through Celite®. The filtrate was extracted with ethyl acetate and the organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 1:6 ethyl acetate:hexanes to give 368.5 mg (20%) of ethyl 6-bromo-7-fluoro-2-quinolinecarboxylate as a solid. 1H NMR (400 MHz, d6-DMSO): δ 8.63 (d, J=8 Hz, 1H), 8.58 (d, J=9 Hz, 1H), 8.15 (s, 1H), 8.13 (s, 1H), 4.42 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz, 3H). ESI-LCMS m/z 297 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. customcarefully quenched with saturated sodium bicarbonate
  3. additionEthyl acetate was added
  4. filtrationthe mixture was filtered through Celite®
  5. extractionThe filtrate was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 1:6 ethyl acetate

Sources & evidence

ORD record
ord-fe76bb7b0a9d4bff9e2e69421a95f0e5
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

Loading…