Ethyl Acetate → N-[5,6-dibromo-1H-indazol-3-yl]butanamide

HRID 497668Notes

Reaction equation

HRID 497668 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[Br:29])[N:25](COCC[Si](C)(C)C)[N:24]=[C:23]2[NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42].C(OCC)(=O)C>O1CCCC1>[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[Br:29])[NH:25][N:24]=[C:23]2[NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319520HCID 22319520, compound

Product 1

HCID 22319616N-[5,6-dibromo-1H-indazol-3-yl]butanamideYield 62.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

12.2 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 60 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours; after cooling, 75 cm3 of ethyl acetate are added and the organic phase is washed successively with 100 cm3 of saturated sodium hydrogen carbonate solution and then with 75 cm3 of saturated sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.) to give 1.6 g of crude product, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 20 cm3 of diisopropyl ether, filtered off, washed with 2×10 cm3 of diisopropyl ether and dried (90 Pa; 45° C.) to give 460 mg of N-[5,6-dibromo-1H-indazol-3-yl]butanamide in the form of bluish crystals melting at 250° C.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperatureafter cooling
  3. washthe organic phase is washed successively with 100 cm3 of saturated sodium hydrogen carbonate solution
  4. customThe organic phase is separated out
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  8. customto give 1.6 g of crude product, which
  9. customis purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. filtrationfiltered off
  14. washwashed with 2×10 cm3 of diisopropyl ether
  15. customdried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-ede23ffc1701484481043e96fd710f74
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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