Toluene → HCID 59556189, compound

HRID 1016065Notes

Reaction equation

HRID 1016065 reaction equation
[CH3:1][C:2]([O-:5])([CH3:4])[CH3:3].[Na+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[C:13]1([CH3:19])[CH:18]=[CH:17][CH:16]=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:5][C:2]1([C:4]2[CH:16]=[CH:17][C:18]([N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:13][CH:19]=2)[CH2:3][CH2:3][C:2](=[O:5])[CH2:1][CH2:1]1

Participants

5

Reactant 3

HCID 1140Toluene2×HCID 8083MorpholineHCID 23676156Sodium t-butoxide

Product 1

HCID 59556189HCID 59556189, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To an oven-dried flask was charged with Pd2(dba)3 (4.6 mg, 0.005 mmol), (o-biphenyl)P(t-Bu)2 (6.0 mg, 0.02 mmol, 2 mol %), and NaOt-Bu (135 mg, 1.4 mmol). The flask was evacuated and backfilled with nitrogen and then capped with a rubber septum. Toluene (0.5 mL), the aryl iodide (360 mg, 1.0 mmol), morpholine (102 mg, 1.2 mmol), and additional toluene (0.5 mL) were added. The mixture was stirred at room temperature until the starting aryl iodide had been completely consumed as judged by TLC analysis. The mixture was diluted with ether (20 mL), filtered through Celite, and concentrated in vacuo. The crude residue was dissolve in THF (1 mL) and was treated with 5% HCl (9 mL) at rt for 14 h. The mixture was neutralized with 1 N NaOH to pH 7, concentrated on rotovap, and then extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with saline solution (2×50 mL), dried over sodium sulfate, concentrated in vacuo. The resulting residue was chromatographed on silica gel, eluting with hexane/ethyl acetate (100/0 to 0/100), to provide the desired compound (100 mg, 36% for the two steps). LCMS: 276.2 (M+H+, 100%). 1H NMR: (CDCl3) δ 7.42 (d, 2H), 6.88 (d, 2H), 3.99-3.94 (m, 4H), 3.86-3.84 (m, 4H), 3.16-3.13 (m, 4H).

Workup

  1. customThe flask was evacuated
  2. customcapped with a rubber septum
  3. customhad been completely consumed
  4. additionThe mixture was diluted with ether (20 mL)
  5. filtrationfiltered through Celite
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude residue was dissolve in THF (1 mL)
  8. additionwas treated with 5% HCl (9 mL) at rt for 14 h
  9. concentrationconcentrated on rotovap
  10. extractionextracted with EtOAc (2×50 mL)
  11. washwashed with saline solution (2×50 mL)
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe resulting residue was chromatographed on silica gel
  15. washeluting with hexane/ethyl acetate (100/0 to 0/100)

Sources & evidence

ORD record
ord-e275a371cbaa486ebb6dfa3a2de2f444
Source dataset
uspto-grants-2011_07
Patent number
US07985730B2

Reaction notes

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