Water → 7-Cyclopropyl-8-fluoro-2-methylquinoline

HRID 338998Notes

Reaction equation

HRID 338998 reaction equation
Br[C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[Br-].[CH:15]1([Zn+])[CH2:17][CH2:16]1.C(OCC)(=O)C.O>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:15]1([C:2]2[C:11]([F:12])=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([CH3:13])=[N:9]3)=[CH:4][CH:3]=2)[CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 709833547-Bromo-8-fluoro-2-methylquinolineHCID 178419765HCID 178419765, compound

Product 1

HCID 709843967-Cyclopropyl-8-fluoro-2-methylquinolineYield 80.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-bromo-8-fluoro-2-methylquinoline (0.15 g, 0.63 mmol), Pd(PPh3)4 (0.072 g, 0.063 mmol) and 0.5 M cyclopropylzinc(II) bromide (2.50 ml, 1.25 mmol) in THF was stirred at reflux for 12 hours. After cooling to ambient temperature, ethyl acetate (20 mL) and water (5 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane/ethyl acetate 2:1) to give 7-cyclopropyl-8-fluoro-2-methylquinoline (0.10 g, 80.3%) as a solid.

Workup

  1. temperatureat reflux for 12 hours
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-9f4abf69a5a845c4b6e7c14e9f4c1390
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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