Triethylamine → HCID 68654609, compound

HRID 229250Notes

Reaction equation

HRID 229250 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[C:4]([F:23])[CH:3]=1.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26].CCN(CC)CC>CN(C=O)C.O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:29]([O:28][C:24](=[O:27])[CH:25]=[CH:26][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[C:4]([F:23])[CH:3]=1)[CH3:30]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 68654303HCID 68654303, compound

Product 1

HCID 68654609HCID 68654609, compoundYield 81%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[(4-bromo-2-fluoro-phenyl)-cycloheptylidene-methyl]-phenol (175) (1.0 g, 2.66 mmol) in DMF (27 mL) was added ethyl acrylate (2.9 mL, 26.6 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.187 g, 0.266 mmol) and Et3N (2.2 mL, 15.99 mmol). The reaction mixture was heated at 100° C. for 20 h. The reaction mixture was cooled to room temperature and diluted with water (10 mL) and EtOAc (20 mL). The aqueous mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was loaded onto silica gel and purified by flash chromatography with a hexanes:EtOAc gradient (100:0 to 90:10) to give 0.85 g (81%) of the title compound 176 as an oil. 1H NMR (400 MHz, DMSO-d6): δ 1.22 (t, J=7.1 Hz, 3H), 1.48-1.51 (m, 8H), 2.07-2.10 (m, 2H), 2.25 (s, 2H), 4.13-4.18 (m, 2H), 6.61-6.66 (m, 3H), 6.92 (d, J=8.6 Hz, 2H), 7.20 (t, J=7.8 Hz, 1H), 7.47 (d, J=6.6 Hz, 1H), 7.56-7.60 (m, 2H), 9.32 (s, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe aqueous mixture was transferred to a separatory funnel
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash chromatography with a hexanes

Sources & evidence

ORD record
ord-3528803d58dc47cab5d8002bec31b5ac
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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