Ethyl Acetate → HCID 22319490, compound

HRID 497701Notes

Reaction equation

HRID 497701 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][C:35]=2[C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:38][CH:37]=2)[N:32](COCC[Si](C)(C)C)[N:31]=[C:30]3[NH:58][C:59](=[O:63])[CH2:60][CH2:61][CH3:62])=[CH:23][CH:22]=1)[CH3:20].C(OCC)(=O)C>O1CCCC1>[CH2:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][C:35]=2[C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[CH:38][CH:37]=2)[NH:32][N:31]=[C:30]3[NH:58][C:59](=[O:63])[CH2:60][CH2:61][CH3:62])=[CH:23][CH:22]=1)[CH3:20]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319589HCID 22319589, compound

Product 1

HCID 22319490HCID 22319490, compoundYield 98.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

8.3 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 850 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 50 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 2×100 cm3 of saturated sodium hydrogen carbonate solution and 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 1.5 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 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); the residue is dried (90 Pa; 45° C.) to give 660 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of grey crystals.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperatureafter cooling
  3. washthe organic phase is washed successively with 2×100 cm3 of saturated sodium hydrogen carbonate solution and with 75 cm3 of saturated sodium chloride 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 1.5 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 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. customthe residue is dried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-3b164e070a164adc8c67945923da48fb
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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