Tetrahydrofuran → 7-Chloro-2-[5-(2-methoxycarbonyl-2-methylpropyl)benzofuran-2-yl]-quinoline

HRID 2258521Notes

Reaction equation

HRID 2258521 reaction equation
C([N-]C(C)C)(C)C.[Li+].O1CCCC1.[CH3:14][CH:15]([CH3:20])[C:16]([O:18][CH3:19])=[O:17].[Cl:21][C:22]1[CH:31]=[C:30]2[C:25]([CH:26]=[CH:27][C:28]([C:32]3[O:33][C:34]4[CH:40]=[CH:39][C:38]([CH2:41]Cl)=[CH:37][C:35]=4[CH:36]=3)=[N:29]2)=[CH:24][CH:23]=1>CN(C)P(=O)(N(C)C)N(C)C.CCCCCC>[Cl:21][C:22]1[CH:31]=[C:30]2[C:25]([CH:26]=[CH:27][C:28]([C:32]3[O:33][C:34]4[CH:40]=[CH:39][C:38]([CH2:41][C:15]([C:16]([O:18][CH3:19])=[O:17])([CH3:20])[CH3:14])=[CH:37][C:35]=4[CH:36]=3)=[N:29]2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11039Methyl isobutyrateHCID 2724682Lithium diisopropylamideHCID 229221267-Chloro-2-(5-chloromethylbenzofuran-2-yl)quinoline

Product 1

HCID 229221907-Chloro-2-[5-(2-methoxycarbonyl-2-methylpropyl)benzofuran-2-yl]-quinolineYield 9.3%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent2×

Procedure

To a cooled suspension of lithium diisopropylamide {(1.45 mM tetrahydrofuran and n-hexane solution), 3.1 ml} and methyl 2-methylpropionate (0.5 g), dried hexamethylphosphoric triamide (0.5 ml) was added at -78° C. and the mixture was stirred for 10 minutes at the same temperature. Subsequently, 7-chloro-2-(5-chloromethylbenzofuran-2-yl)quinoline (6.43 g) was added to the mixture. After being stirred for 30 minutes at the same temperature, additive hexamethylphosphoric triamide (1.36 ml) was added to the mixture. The reaction temperature was gradually elevated to -10° C. for 1 hour. The resulting mixture was poured into ice-water and extracted with chloroform. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel (100 g) and eluted with n-hexane, successively 10% ethyl acetate in n-hexane and toluene. The fractions containing object compound were combined and concentrated under reduced pressure. The residue was dissolved in chloroform and n-hexane was added to the solution. The resulting precipitates were collected by filtration and dried to give 7-chloro-2-[5-(2-methoxycarbonyl-2-methylpropyl)benzofuran-2-yl]-quinoline (0.18 g).

Workup

  1. additionwas added at -78° C.
  2. additionwas added to the mixture
  3. waitThe reaction temperature was gradually elevated to -10° C. for 1 hour
  4. extractionextracted with chloroform
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluted with n-hexane, successively 10% ethyl acetate in n-hexane and toluene
  9. additionThe fractions containing object compound
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in chloroform
  12. additionn-hexane was added to the solution
  13. customThe resulting precipitates
  14. filtrationwere collected by filtration
  15. customdried

Sources & evidence

ORD record
ord-93117cfe0fe94338906ba46fec0026b1
Source dataset
uspto-grants-1997_08
Patent number
US05661159

Reaction notes

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