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

HRID 497624Notes

Reaction equation

HRID 497624 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]([F:52])([F:51])[O:21][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.C(OCC)(=O)C>O1CCCC1>[F:52][C:20]([F:19])([F:51])[O:21][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][NH:34]3)=[CH:30][CH:29]=2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319666N-[6-[4-(trifluoromethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 22319555N-(6-(4-(trifluoromethoxy)phenyl)-1H-indazol-3-yl)butyramide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

12.1 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1 g of N-[6-[4-(trifluoromethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran. The reaction medium is heated at about 66° C. for 18 hours, the heating is then stopped and 75 cm3 of ethyl acetate are added. This mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and then concentrated under reduced pressure (2 kPa; 50° 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 2.5 cm), eluting with an ethyl acetate/cyclohexane mixture (60/40 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); the residue is taken up in 10 cm3 of diisopropyl ether, filtered on a sinter funnel and then washed successively with 10 cm3 of diisopropyl ether and then with 2×2 cm3 of ethyl acetate. After drying (90 Pa; 50° C.), 520 mg of N-[6-[4-(trifluoromethoxy)phenyl]-1H-indazol-3-yl]butanamide are obtained in the form of a white product melting at 234° C.

Workup

  1. washThis mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution
  2. customThe organic phase is separated out
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (2 kPa; 50° C.)
  6. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  7. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with an ethyl acetate/cyclohexane mixture (60/40 by volume)
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. filtrationfiltered on a sinter funnel
  11. washwashed successively with 10 cm3 of diisopropyl ether
  12. dry with materialAfter drying (90 Pa; 50° C.), 520 mg of N-[6-[4-(trifluoromethoxy)phenyl]-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-2fcf28f0b56648d5b30e0cd30e50bda8
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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