Imidazole → HCID 58913114, compound

HRID 1296679Notes

Reaction equation

HRID 1296679 reaction equation
[OH:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[O:10][C:9](=[O:19])[C:8]=2[C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[C:32](Cl)(=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34].N1C=CN=C1>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:18][O:17][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([CH2:6][C:5]3[CH:30]=[CH:31][C:2]([O:1][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:3][CH:4]=3)=[C:8]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:22][CH:21]=3)[C:9](=[O:19])[O:10]2)=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 795Imidazole2×HCID 62493Pivaloyl chloride2×HCID 22994355HCID 22994355, compound

Product 1

HCID 58913114HCID 58913114, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(4-hydroxybenzyl)-7-methoxy-3-(4-trifluoromethyl-phenyl)-chromen-2-one (800 mg, 1.88 mmol), pivaloyl chloride (577 μL, 4.69 mmol), imidazole (268 mg, 3.94 mmol) and DMAP (344 mg, 2.81 mmol) in DMF (10 mL) was stirred at room temperature for 18 h. Additional portions of imidazole (268 mg, 3.94 mmol), DMAP (344 mg, 2.81 mmol) and pivaloyl chloride (577 μL, 4.69 mmol) were added and stirring was continued for a further 20 h, for a total reaction time of 38 h. The solvent was removed in vacuo, the residue was dissolved in AcOEt and the organic layer was washed with H2O. The aq layer was extracted with AcOEt (2×) and the combined organic layers were washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The resultant residue was purified using flash chromatography (silica gel, 5:1 hexanes:AcOEt) to provide the title compound as a white solid (820 mg, 86%). 1H NMR (300 MHz, CDCl3) δ 7.64 (d, J=8.0 Hz, 2H), 7.43–7.37 (m, 3H), 7.08–7.02 (m, 2H), 7.00–6.93 (m, 2H), 6.88 (d, J=2.5 Hz, 1H), 6.77 (dd, J=2.5, 8.8 Hz, 1H), 4.04 (s, 2H), 3.87 (s, 3H), 1.34 (s, 9H); MS (ESI) m/z 511.0 (M+H)+; HPLC tR 7.58 min.

Workup

  1. stirringstirring
  2. waitwas continued for a further 20 h, for a total reaction time of 38 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in AcOEt
  5. washthe organic layer was washed with H2O
  6. extractionThe aq layer was extracted with AcOEt (2×)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent was removed in vacuo
  10. customThe resultant residue was purified

Sources & evidence

ORD record
ord-bd3ea601c81648f9b08fee20e384aebf
Source dataset
uspto-grants-2007_07
Patent number
US07247646B2

Reaction notes

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