Triethylamine → 1,1-Dimethylethyl(2E)-3-{4-[cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoate

HRID 2100025Notes

Reaction equation

HRID 2100025 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[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)=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:25])[CH:23]=[CH2:24].C(N(CC)CC)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.II.CC(O)=O>CC([O-])=O.CC([O-])=O.[Pd+2].O.CCOC(C)=O.CC#N>[C:16]1(=[C:8]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[C:5]2[CH:6]=[CH:7][C:2](/[CH:24]=[CH:23]/[C:22]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:3][CH:4]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

10

Reactant 5

HCID 8471Triethylamine2×HCID 15458tert-Butyl acrylate2×HCID 80271Tri-o-tolylphosphine2×HCID 23287334II acetateHCID 686545334-[(4-Bromophenyl)(cyclohexylidene)methyl]phenol

Product 1

HCID 689777101,1-Dimethylethyl(2E)-3-{4-[cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoateYield 76%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a round-bottomed flask were added 4-[(4-bromophenyl)(cyclohexylidene)methyl]phenol (6) (0.465 g, 1.35 mmol), tert-butyl acrylate (0.58 mL, 0.508 g, 3.96 mmol, 2.9 eq), Pd(OAc)2 (0.03 g, 0.134 mmol, 0.1 eq), triethylamine (0.54 mL, 0.39 g, 3.87 mmol, 2.9 eq), P(o-tolyl)3 (0.08 g, 0.26 mmol, 0.19 eq), and CH3CN (6 mL). The reaction mixture was heated overnight at 75° C. with stirring under a nitrogen atmosphere. Thin layer chromatography indicated the reaction was not complete. To the reaction mixture were added P(o-tolyl)3 (0.087 g, 0.29 mmol, 0.21 eq), tert-butyl acrylate (0.58 mL, 0.51 g, 3.96 mmol, 2.9 eq), paladium II acetate (0.033 g, 0.147 mmol), triethylamine (0.54 mL, 0.39 g, 3.87 mmol), and CH3CN (2 mL). The reaction mixture was heated at 75° C. with stirring under a nitrogen atmosphere for three days. The reaction mixture was allowed to cool to room temperature and transferred to a separatory funnel with the aid of EtOAc and H2O. The layers were separated and the organic phase was washed with brine. The organic solution was dried over MgSO4, filtered, and the filtrate was concentrated to give the crude product as an oil. The crude product was purified by flash chromatography on silica gel with hexanes:EtOAc (100:0 to 50:50) to give 0.40 g (76%) of compound 7 as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 1.45 (s, 9 H), 1.52 (m, 6 H), 2.14 (m, 4 H), 6.43 (d, J=15.9 Hz, 1 H), 6.66 (d, J=8.5 Hz, 2 H), 6.84 (d, J=8.4 Hz, 2 H), 7.05 (d, J=8.1 Hz, 2 H), 7.48 (d, J=15.9 Hz, 1 H), 7.57 (d, J=8.1 Hz, 2 H), 9.31 (s, 1 H). The sample was silated prior to EI analysis. HRMS (EI) Calcd for C29H38O3Si: 462.2590 (M+). Found: 462.2592.

Workup

  1. temperatureThe reaction mixture was heated at 75° C.
  2. stirringwith stirring under a nitrogen atmosphere for three days
  3. temperatureto cool to room temperature
  4. customThe layers were separated
  5. washthe organic phase was washed with brine
  6. dry with materialThe organic solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customto give the crude product as an oil
  10. customThe crude product was purified by flash chromatography on silica gel with hexanes:EtOAc (100:0 to 50:50)

Sources & evidence

ORD record
ord-3f316b384cbb485c87f624d640178956
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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