Potassium Carbonate → methyl 7-(4-(4-methoxyphenyl)-1H-imidazol-1-yl)-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate

HRID 1911040Notes

Reaction equation

HRID 1911040 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[O:6][CH2:7][CH2:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:11])[C:4]=2[CH:3]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:27]=[CH:28][NH:29][CH:30]=2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>[Cu]I.CN(C=O)C>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:27]=[CH:28][N:29]([C:2]3[CH:17]=[CH:16][C:5]4[O:6][CH2:7][CH2:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:11])[C:4]=4[CH:3]=3)[CH:30]=2)=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 71061088Methyl 7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylateHCID 178418716HCID 178418716, compound

Product 1

HCID 71062477methyl 7-(4-(4-methoxyphenyl)-1H-imidazol-1-yl)-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To an oven dried microwave vial was added methyl 7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate from step H5 (200 mg, 0.673 mmol), 4-(4-methoxyphenyl)-1H-imidazole (141 mg, 0.808 mmol), potassium carbonate (186 mg, 1.35 mmol) and copper(I) iodide (72.9 mg, 0.383 mmol). The vial was capped with a septum and the system was degassed and flushed with nitrogen (3×). Then 2,2,6,6-tetramethylheptane-3,5-dione (0.194 mL, 0.944 mmol) and DMF (5 mL) were added and the reaction mixture was degassed and flushed with nitrogen (3×). The vial was sealed and place in a pre-heated oil bath at 120° C. The reaction mixture was stirred at 120° C. for 20 h. The reaction was poured into water to afford a blue mixture that was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography (30-100% EtOAc/hexanes) to afford methyl 7-(4-(4-methoxyphenyl)-1H-imidazol-1-yl)-5-methyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate (180 mg, 0.461 mmol, 69% yield). LCMS (M+H)+=391.1. 1H NMR (500 MHz, chloroform-d) δ 7.88 (br. s., 1H), 7.77 (d, J=7.2 Hz, 2H), 7.39-7.33 (m, 3H), 7.18 (d, J=8.4 Hz, 1H), 6.94 (d, J=7.5 Hz, 2H), 4.59 (t, J=6.0 Hz, 2H), 3.87-3.82 (m, 6H), 2.57 (t, J=5.9 Hz, 2H), 2.49 (s, 3H).

Workup

  1. customTo an oven dried microwave vial
  2. customThe vial was capped with a septum
  3. customthe system was degassed
  4. customflushed with nitrogen (3×)
  5. customthe reaction mixture was degassed
  6. customflushed with nitrogen (3×)
  7. customThe vial was sealed
  8. customat 120° C
  9. additionThe reaction was poured into water
  10. customto afford a blue mixture that
  11. extractionwas extracted with ethyl acetate
  12. washThe combined organic layers were washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe crude material was purified by silica gel column chromatography (30-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-dfd892c7bbcd46aabe24c840ebd26f2e
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

Loading…