Ethyl Acetoacetate → Ethyl 6-bromo-2-methylquinoline-3-carboxylate

HRID 2423523Notes

Reaction equation

HRID 2423523 reaction equation
[Sn](Cl)Cl.[Br:4][C:5]1[CH:6]=[CH:7][C:8]([N+:13]([O-])=O)=[C:9]([CH:12]=1)[CH:10]=O.O=[C:17]([CH3:24])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20]>C(OCC)C.C(O)C.[Cl-].[Zn+2].[Cl-]>[Br:4][C:5]1[CH:12]=[C:9]2[C:8](=[CH:7][CH:6]=1)[N:13]=[C:17]([CH3:24])[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:10]2

Participants

7

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24479Stannous ChlorideHCID 972335-Bromo-2-nitrobenzaldehyde

Product 1

HCID 17039982Ethyl 6-bromo-2-methylquinoline-3-carboxylateYield 55%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 702EthanolSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

A 2.2 M solution of zinc(II)chloride (9.88 mL, 21.74 mmol) in diethyl ether was added to tin(II)chloride (4.12 g, 21.74 mmol) and activated 4 Å molecular sieve pellets (1.00 g) in ethanol (10 mL) under argon. Then, 5-bromo-2-nitro-benzaldehyde (1.00 g, 4.35 mmol) and ethyl 3-oxobutanoate (594.0 mg, 4.56 mmol) in ethanol (12 mL) were added to the reaction mixture via canula. The mixture was heated at 70° C. in an oil bath for three 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 697.9 mg (55%) of ethyl 6-bromo-2-methyl-3-quinolinecarboxylate as a solid. 1H NMR (400 MHz, d6-DMSO): δ 8.84 (s, 1H), 8.42 (d, J=2 Hz, 1H), 7.95 (dd, J=9, 2 Hz, 1H), 7.91 (d, J=9 Hz, 1H), 4.38 (q, J=7 Hz, 2H), 2.84 (s, 3H), 1.37 (t, J=7 Hz, 3H). ESI-LCMS m/z 294 (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-607504c5d9ff4e9997925c4278707673
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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