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

HRID 497608Notes

Reaction equation

HRID 497608 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]1([CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:41]=[C:40]4[C:36]([C:37]([NH:50][C:51](=[O:55])[CH2:52][CH2:53][CH3:54])=[N:38][N:39]4COCC[Si](C)(C)C)=[CH:35][CH:34]=3)=[CH:29][CH:28]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(OCC)(=O)C>O1CCCC1>[C:19]1([CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:41]=[C:40]4[C:36]([C:37]([NH:50][C:51](=[O:55])[CH2:52][CH2:53][CH3:54])=[N:38][NH:39]4)=[CH:35][CH:34]=3)=[CH:29][CH:28]=2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 10029506N-[6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 10452673N-(6-(4-(benzyloxy)phenyl)-1H-indazol-3-yl)butyramide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

14 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1.2 g of N-[6-[4-(phenylmethoxy)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 17 hours. The heating is then stopped and 75 cm3 of ethyl acetate are added. This mixture is washed with 50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and evaporated 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 3.5 cm), eluting with cyclohexane/ethyl acetate (80/20 by volume) and collecting 30 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 2×2 cm3 of diisopropyl ether. This mixture is filtered through a sinter funnel to give, after drying (90 Pa; 50° C.), 220 mg of N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of a white solid melting at 220° C.

Workup

  1. washThis mixture is washed with 50 cm3 of saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered through a sinter funnel
  4. customevaporated under reduced pressure (2 kPa; 50° C.)
  5. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  6. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with cyclohexane/ethyl acetate (80/20 by volume)
  7. customcollecting 30 cm3 fractions
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. filtrationThis mixture is filtered through a sinter funnel
  11. customto give
  12. dry with materialafter drying (90 Pa; 50° C.), 220 mg of N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of a white solid melting at 220° C.

Sources & evidence

ORD record
ord-62f5110f43bc437ea253121cbc367b9d
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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