Ethyl Acetate → HCID 22319694, compound

HRID 497628Notes

Reaction equation

HRID 497628 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:34]=[C:33]3[C:29]([C:30]([NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47])=[N:31][N:32]3COCC[Si](C)(C)C)=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.C(OCC)(=O)C>O1CCCC1>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:34]=[C:33]3[C:29]([C:30]([NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47])=[N:31][NH:32]3)=[CH:28][CH:27]=2)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319639HCID 22319639, compound

Product 1

HCID 22319694HCID 22319694, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

8.1 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 580 mg of N-[6-(4-fluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran, and the reaction medium is heated at about 66° C. for 22 hours. The heating is then stopped, 75 cm3 of ethyl acetate are added and the resulting mixture is washed with 50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm 3 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 concentrated to dryness 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 a cyclohexane/ethyl acetate mixture (40/60 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 and washed successively with 5 cm3 of diisopropyl ether and 2×3 cm3 of ethyl acetate; after drying (90 Pa; 50° C.), 250 mg of N-[6-(4-fluorophenyl)-1H-indazol-3-yl]butanamide are thus obtained in the form of a white product melting at 232° C.

Workup

  1. washthe resulting mixture is washed with 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 to dryness 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 a cyclohexane/ethyl acetate mixture (40/60 by volume)
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. filtrationfiltered
  11. washwashed successively with 5 cm3 of diisopropyl ether and 2×3 cm3 of ethyl acetate
  12. dry with materialafter drying (90 Pa; 50° C.), 250 mg of N-[6-(4-fluorophenyl)-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-06bea6b602504c679c988825849cbaa8
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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