Potassium tert-butoxide → HCID 44582642, compound

HRID 222463Notes

Reaction equation

HRID 222463 reaction equation
C([SiH2][O:6][C:7](C1C=CC=CC=1)(C1C=CC=CC=1)[C:8]1[CH:20]=[CH:19][C:11]2[C:12]([CH2:15][C:16]([NH2:18])=[O:17])=[CH:13][O:14][C:10]=2[CH:9]=1)(C)(C)C.C([O:35][C:36](=O)[C:37]([C:39]1[C:47]2[C:42](=[CH:43][CH:44]=[C:45]([F:48])[CH:46]=2)[N:41]([CH3:49])[CH:40]=1)=O)C.CC(C)([O-])C.[K+]>C1COCC1>[F:48][C:45]1[CH:46]=[C:47]2[C:42](=[CH:43][CH:44]=1)[N:41]([CH3:49])[CH:40]=[C:39]2[C:37]1[C:36](=[O:35])[NH:18][C:16](=[O:17])[C:15]=1[C:12]1[C:11]2[CH:19]=[CH:20][C:8]([CH2:7][OH:6])=[CH:9][C:10]=2[O:14][CH:13]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 68526851HCID 68526851, compoundHCID 131729790HCID 131729790, compound

Product 1

HCID 44582642HCID 44582642, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the 2-[6-(tert-butyl-diphenyl-silanyloxymethyl)-benzofuran-3-yl]-acetamide (0.36 g, 0.81 mmol) and (5-fluoro-1-methyl-1H-indol-3-yl)-oxo-acetic acid ethyl ester (0.20 g, 0.81 mmol) in dry THF (8 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (6.49 mL) at 0° C. The reaction was stirred for 30 min, allowed to warm to room temperature and stirred for additional 30 min. The reaction was quenched with water, and diluted with EtOAc. The organic solution was washed with brine, then dried over Na2SO4 and concentrated. The residue was dissolved in THF and a 1.0 M solution of TBAF in THF (1.22 mL) was added at room temperature. The mixture was stirred for 2 h. The solution was quenched with NH4Cl and stirred for 5 min. The solvent was removed and the residue was dissolved in dichloromethane and washed twice with water and brine. The organic phase was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (methanol:dichloromethane; 5:95 to 1:9) to give the 3-(5-fluoro-1-methyl-1H-indol-3-yl)-4-(6-hydroxymethyl-benzofuran-3-yl)-pyrrole-2,5-dione as an orange solid (0.23 g, 72%). 1H NMR (DMSO-d6, 400 MHz) 3.88 (s, 3H), 4.52 (d, J=5.7 Hz, 2H), 5.24 (t, J=5.7 Hz, 1H), 6.53 (dd, J=2.3, 10.3 Hz, 1H), 6.84 (d, J=8.1 Hz, 1H), 6.89 (d, J=8.2 Hz, 1H), 6.95 (dt, J=2.4, 9.1 Hz, 1H), 7.49 (dd, J=4.5, 9.5 Hz, 1H), 7.54 (s, 1H), 8.02 (s, 1H), 8.24 (s, 1H), 11.19 (s, 1H). 13C NMR (DMSO-d6, 100 MHz) 33.7, 63.1, 104.27, 104.31, 103.1, 106.3, 109.4, 110.5, 110.8, 111.7, 112.2, 112.3, 121.5, 121.9, 122.9, 124.5, 126.4, 126.5, 132.6, 133.9, 136.2, 140.6, 147.4, 154.9, 156.5, 172.2, 172.5.

Workup

  1. stirringstirred for additional 30 min
  2. customThe reaction was quenched with water
  3. additiondiluted with EtOAc
  4. washThe organic solution was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in THF
  8. additiona 1.0 M solution of TBAF in THF (1.22 mL) was added at room temperature
  9. stirringThe mixture was stirred for 2 h
  10. customThe solution was quenched with NH4Cl
  11. stirringstirred for 5 min
  12. customThe solvent was removed
  13. dissolutionthe residue was dissolved in dichloromethane
  14. washwashed twice with water and brine
  15. dry with materialThe organic phase was dried over Na2SO4
  16. concentrationconcentrated
  17. customThe residue was purified by column chromatography (methanol:dichloromethane; 5:95 to 1:9)

Sources & evidence

ORD record
ord-968fe7151c3b4632a3cd96c71abe29ee
Source dataset
uspto-grants-2012_06
Patent number
US08207216B2

Reaction notes

Loading…