Ethyl Acetate → HCID 59004664, compound

HRID 1668446Notes

Reaction equation

HRID 1668446 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][N:14]1[CH3:18])[C:6]([C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1)=[CH:5]2.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:45][Si](C)(C)C)(C)C.[Li+].C(OCC)(=O)C>O.[OH-].[Na+].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:18][N:14]1[CH2:15][CH2:16][CH2:17][CH:13]1[CH2:12][CH2:11][N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH2:45])=[CH:10][CH:9]=2)[CH:5]=[C:6]1[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 59004600HCID 59004600, compound

Product 1

HCID 59004664HCID 59004664, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

Compound 19 (0.5 g, 1.167 mmol) and tris(dibenzylideneacetone) dipalladium (0) (53.4 mg, 0.058 mmol) were charged to an argon-purged flask fitted with a magnetic stirbar and condenser. Anhydrous tetrahydrofuran (15 mL) was added and stirring begun. Tri-tert-butylphosphine (0.358 mL, 0.1167 mmol, 10 wt % in hexanes) and lithium bis(trimethylsilyl)amide solution (3.501 mL, 3.501 mmol, 1.0 M in THF) were added and the mixture heated to reflux for 2 hours. The solution was cooled to room temperature overnight, diluted with water (15 mL) and 3M sodium hydroxide solution added to adjust pH to 9. Ethyl acetate added and the mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with H2O, brine, dried over magnesium sulphate, filtered, concentrated and the crude residue purified twice via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95) to afford dark red solid 20 (102 mg, 24.0%); 1H NMR (DMSO-d6) δ 8.33 (d, 2H, J=8.7 Hz), 7.82 (d, 2H, J=8.8 Hz), 7.25 (d, 1H, J=8.8 Hz), 6.72 (d, 1H, J=1.8 Hz), 6.63 (m, 1H), 6.49 (s, 1H), 4.64 (brs, 2H), 4.25-4.12 (m, 2H), 2.88-2.78 (m, 1H), 1.99 (s, 3H), 1.91 (q, 1H, J=8.8 Hz), 1.84-1.72 (m, 2H), 1.64-1.55 (m, 1H), 1.52-1.35 (m, 3H), 1.30-1.16 (m, 1H); ESI-MS (m/z, %): 365 (M+1, 100%).

Workup

  1. custompurged flask
  2. customfitted with a magnetic stirbar and condenser
  3. additionAnhydrous tetrahydrofuran (15 mL) was added
  4. temperaturethe mixture heated
  5. temperatureto reflux for 2 hours
  6. additionadded
  7. customthe mixture was transferred to a separatory funnel
  8. customthe organic layer collected
  9. extractionThe aqueous layer was further extracted with ethyl acetate
  10. washthe combined organic layers were washed with H2O, brine
  11. dry with materialdried over magnesium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customthe crude residue purified twice via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-f01c22a5e73e4d15b207f2147b482b87
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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