Tetrahydrofuran → HCID 10311016, compound

HRID 1297802Notes

Reaction equation

HRID 1297802 reaction equation
C([Si](C)(C)[O:6][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([C:14]2([C:31]3[CH:36]=[C:35]([CH3:37])[C:34]([O:38][Si](C(C)(C)C)(C)C)=[C:33]([CH3:46])[CH:32]=3)[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([C:23]3[CH:28]=[CH:27][N:26]=[C:25](Cl)[N:24]=3)[C:15]2=[O:30])=[CH:9][C:8]=1[CH3:47])(C)(C)C.C[O-].[Na+].C1C[O:56][CH2:55]C1>CO>[OH:6][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([C:14]2([C:31]3[CH:32]=[C:33]([CH3:46])[C:34]([OH:38])=[C:35]([CH3:37])[CH:36]=3)[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([O:56][CH3:55])[N:24]=3)[C:15]2=[O:30])=[CH:9][C:8]=1[CH3:47]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 58914751HCID 58914751, compound

Product 1

HCID 10311016HCID 10311016, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under an N2 atmosphere, combine 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1-(2-chloro-pyrimidin-4-yl)-1,3-dihydro-indol-2-one and sodium methoxide solution (0.5 M) in methanol (2.0 mL). Add THF (5.0 mL) and stir for 3 h at room temperature. Quench the reaction with saturated aqueous ammonium chloride (25 mL). Add ethyl acetate (25 mL) and separate the layers. Dry the organic layer with sodium sulfate and concentrate in vacuo. Dissolve the crude residue in THF (2 mL), and add a solution of tetrabutylammonium fluoride (1.0 M) in THF (0.84 mL). Stir the reaction at room temperature for 1 h. Quench the reaction with saturated aqueous ammonium chloride (25 mL). Add ethyl acetate (25 mL) and separate the layers. Dry the organic layer with sodium sulfate and concentrate in vacuo. Purify by flash column chromatography eluting with a gradient from 25% to 50% ethyl acetate in hexanes to give 0.289 g (%) of the title compound: mass Spectrum (ion spray): m/z=482(M+1); 1H NMR (DMSO-d6): δ8.67 (d, 1H), 8.29 (s, 2H), 8.21 (d, 1H), 7.36 (td, 1H), 7.30, (dd, 1H), 7.22 (td, 1H), 6.69 (s, 4H), 3.97 (s, 3H), 2.05 (s, 12H).

Workup

  1. customQuench
  2. customthe reaction with saturated aqueous ammonium chloride (25 mL)
  3. customAdd ethyl acetate (25 mL) and separate the layers
  4. dry with materialDry the organic layer with sodium sulfate
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the crude residue in THF (2 mL)
  7. additionadd a solution of tetrabutylammonium fluoride (1.0 M) in THF (0.84 mL)
  8. customthe reaction at room temperature for 1 h
  9. customQuench
  10. customthe reaction with saturated aqueous ammonium chloride (25 mL)
  11. customAdd ethyl acetate (25 mL) and separate the layers
  12. dry with materialDry the organic layer with sodium sulfate
  13. concentrationconcentrate in vacuo
  14. customPurify by flash column chromatography
  15. washeluting with a gradient from 25% to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6dde8b1fb12742209c46fd0186129bf8
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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