Ethyl Acetate → N-(6-(4-nitrophenyl)-1H-indazol-3-yl)butyramide

HRID 497653Notes

Reaction equation

HRID 497653 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:36]=[C:35]3[C:31]([C:32]([NH:45][C:46](=[O:50])[CH2:47][CH2:48][CH3:49])=[N:33][N:34]3COCC[Si](C)(C)C)=[CH:30][CH:29]=2)=[CH:24][CH:23]=1)([O-:21])=[O:20].C(OCC)(=O)C.C(=O)([O-])O.[Na+]>O1CCCC1>[N+:19]([C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:36]=[C:35]3[C:31]([C:32]([NH:45][C:46](=[O:50])[CH2:47][CH2:48][CH3:49])=[N:33][NH:34]3)=[CH:30][CH:29]=2)=[CH:26][CH:27]=1)([O-:21])=[O:20]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 22319698N-[6-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 22319556N-(6-(4-nitrophenyl)-1H-indazol-3-yl)butyramide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
67 °C

Procedure

8.6 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 650 mg of N-[6-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran. The medium is maintained at 67° C. for 18 hours and is then allowed to return to room temperature to add 75 cm3 of ethyl acetate and 75 cm3 of saturated aqueous sodium hydrogen carbonate solution. The organic phase is washed with 50 cm3 of saturated aqueous sodium chloride solution and then with 50 cm3 of water, separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure (2 kPa; 50° C.); the residue is taken up in 10 cm3 of ethyl acetate, filtered off on a sinter funnel and then washed successively with 5 cm3 of ethyl acetate and with 10 cm3 of diisopropyl ether. After drying (90 Pa; 50° C.), 280 mg of N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide are obtained in the form of yellow crystals melting at 250° C.

Workup

  1. customto return to room temperature
  2. washThe organic phase is washed with 50 cm3 of saturated aqueous sodium chloride solution
  3. customwith 50 cm3 of water, separated out
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  7. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 2 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  11. filtrationfiltered off on a sinter funnel
  12. washwashed successively with 5 cm3 of ethyl acetate and with 10 cm3 of diisopropyl ether
  13. dry with materialAfter drying (90 Pa; 50° C.), 280 mg of N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-fddb547189444e9fad32cb665b0886d1
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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