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Dimethylformamide → Ethyl(2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoate

HRID 229220
Notes
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Reaction equation

HRID 229220 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:17]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([F:16])[CH:10]=2)=[CH:4][CH:3]=1.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26].C(N(CC)CC)C.CN(C=O)C>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.CCOC(C)=O.O>[F:16][C:11]1[CH:10]=[C:9]([C:8](=[C:17]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:5]2[CH:6]=[CH:7][C:2](/[CH:26]=[CH:25]/[C:24]([O:28][CH2:29][CH3:30])=[O:27])=[CH:3][CH:4]=2)[CH:14]=[CH:13][C:12]=1[OH:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 686542804-[(4-Bromophenyl)(cycloheptylidene)methyl]-2-fluorophenol

Product 1

HCID 68975839Ethyl(2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoateYield 70%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalyst
HCID 962WaterSolvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a round-bottomed flask were added 4-[(4-bromophenyl)(cycloheptylidene)methyl]-2-fluorophenol (133) (0.30 g, 0.80 mmol), ethyl acrylate (0.88 mL, 8.00 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.056 g, 0.08 mmol), triethylamine (0.56 mL, 4.00 mmol) and DMF (10 mL). The stirred reaction mixture was heated overnight at 100° C. under a nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature and transferred to a separatory funnel with the aid of water and EtOAc (100 mL). The layers were separated and the organic phase was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give reddish brown oil. The crude product was purified by chromatography on a silica gel column eluted with a gradient from hexanes to 15% EtOAc:hexanes to give 0.22 g (70%) of compound 134 as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ 1.33 (t, J=7.1 Hz, 3H), 1.57 (br s, 8H), 2.25-2.35 (m, 4H), 4.25 (q, J=7.1 Hz, 2H), 4.99 (d, J=4.0 Hz, 1H), 6.39 (d, J=15.9 Hz, 1H), 6.75-6.88 (m, 2H), 6.91 (t, J=8.7 Hz, 1H), 7.14 (d, J=8.2 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H), 7.65 (d, J=16.0 Hz, 1H). LCMS (ES): m/z, 395 (M+H)+, 393 (M−H)−.

Workup

  1. customThe stirred reaction mixture
  2. temperatureto cool to room temperature
  3. customThe layers were separated
  4. washthe organic phase was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give
  9. customThe crude product was purified by chromatography on a silica gel column
  10. washeluted with a gradient from hexanes to 15% EtOAc

Sources & evidence

ORD record
ord-7e97be1974074600be08e963229a975c
Source dataset
uspto-grants-2009_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07560589B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes