18-Crown-6 → Methyl-5-(4-acetyl-2-bromo-phenoxy)-nicotinate

HRID 1098742Notes

Reaction equation

HRID 1098742 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.[Br:12][C:13]1[CH:14]=[C:15]([C:20](=[O:22])[CH3:21])[CH:16]=[CH:17][C:18]=1F.C1OCCOCCOCCOCCOCCOC1.[F-].[K+]>C(#N)C>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([O:10][C:18]2[CH:17]=[CH:16][C:15]([C:20](=[O:22])[CH3:21])=[CH:14][C:13]=2[Br:12])[CH:7]=[N:6][CH:5]=1

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 705081-(3-Bromo-4-fluorophenyl)ethan-1-oneHCID 354317Methyl 5-hydroxypyridine-3-carboxylateHCID 522689Potassium Fluoride

Product 1

HCID 59506149Methyl-5-(4-acetyl-2-bromo-phenoxy)-nicotinateYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl-5-hydroxynicotinate (1.0 g, 6.53 mmol), 3′-bromo-4′-fluoroacetophenone (1.42 g, 6.53 mmol), 18-crown-6 (155.3 mg, 0.59 mmol) and potassium fluoride (40 wt. % on alumina, 996 mg, 6.86 mmol) were dissolved in ACN (10 mL). The reaction was refluxed for three days. After cooling the mixture was quenched with 2N aqueous potassium carbonate solution, extracted with ether, dried with sodium sulphate, filtered, evaporated and purified by silica gel chromatography (ethyl acetate:n-heptane 1:4). 635 mg (yield: 28%) of the pure compound was obtained.

Workup

  1. temperatureThe reaction was refluxed for three days
  2. temperatureAfter cooling the mixture
  3. customwas quenched with 2N aqueous potassium carbonate solution
  4. extractionextracted with ether
  5. dry with materialdried with sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by silica gel chromatography (ethyl acetate:n-heptane 1:4)

Sources & evidence

ORD record
ord-1756328d1ced41c59561b11efe9274f9
Source dataset
uspto-grants-2012_03
Patent number
US08143242B2

Reaction notes

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