Tetrabutylammonium Fluoride → N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

HRID 497657Notes

Reaction equation

HRID 497657 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]1([CH2:25][O:26][C:27]2[CH:28]=[C:29]([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:30]=[CH:31][CH:32]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1.C(OCC)(=O)C>[C:19]1([CH2:25][O:26][C:27]2[CH:28]=[C:29]([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:30]=[CH:31][CH:32]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 22319536N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 22319688N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamideYield 57.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2.9 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1 g of N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide, described previously, in 20 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours. The reaction medium is diluted with 100 cm3 of ethyl acetate and the organic phase is washed successively with 50 cm3 of saturated sodium hydrogen carbonate solution, with 2×50 cm3 of water and with 50 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 under reduced pressure (2 kPa; 50° C.). The crude product obtained 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 a cyclohexane/ethyl acetate gradient (70/30 to 40/60 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); 0.43 g of N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide is obtained in the form of a white powder.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. washthe organic phase is washed successively with 50 cm3 of saturated sodium hydrogen carbonate solution, with 2×50 cm3 of water and with 50 cm3 of saturated sodium chloride solution
  3. customThe organic phase is separated out
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (2 kPa; 50° C.)
  7. customThe crude product obtained
  8. customis purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate gradient (70/30 to 40/60 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-87c332f43d4b42afa6de632aedc53f92
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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