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

HRID 2100028Notes

Reaction equation

HRID 2100028 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)=[CH:4][CH:3]=1.[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:26])[CH:24]=[CH2:25].CCN(CC)CC.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>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:4]=[CH:3][C:2](/[CH:25]=[CH:24]/[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:7][CH:6]=2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 686541254-[(4-Bromophenyl)(cycloheptylidene)methyl]phenol

Product 1

HCID 689772221,1-Dimethylethyl (2E)-3-{4-[cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoateYield 98.4%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
75 °C

Procedure

To a round-bottomed flask were added 4-[(4-bromophenyl)(cycloheptylidene)methyl]phenol (9) (4.0 g, 11.2 mmol), t-butyl acrylate (7.2 mL, 6.3 g, 49.2 mmol, 4.4 eq), Pd(OAc)2 (0.52 g, 2.3 mmol, 0.21 eq), Et3N (9.5 mL, 6.90 g, 68.2 mmol, 6.1 eq), P(o-tolyl)3 (1.3 g, 4.2 mmol, 0.38 eq), and CH3CN (100 mL). The reaction mixture was heated overnight at 75° C. with stirring under a nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature and then transferred to a separatory funnel with the aid of EtOAc and H2O. The layers were separated, and the organic phase washed with brine, dried (MgSO4), filtered, and the filtrate was concentrated to give the crude product as a red-orange oil. The crude product was purified by flush chromatography on silica gel with hexanes:EtOAc (9:1 to 4:1) to give 4.46 g (98%) of compound 10 as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 1.45 (s, 9 H), 1.50 (m, 8 H), 2.21 (m, 4 H), 6.42 (d, J=16.1 Hz, 1 H), 6.65 (d, J=8.4 Hz, 2 H), 6.90 (d, J=8.4 Hz, 2 H), 7.10 (d, J=8.2 Hz, 2 H), 7.48 (d, J=15.9 Hz, 1 H), 7.57 (d, J=8.1 Hz, 2 H), 9.28 (s, 1 H).

Workup

  1. temperatureto cool to room temperature
  2. customThe layers were separated
  3. washthe organic phase washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give the crude product as a red-orange oil
  8. customThe crude product was purified
  9. customby flush chromatography on silica gel with hexanes:EtOAc (9:1 to 4:1)

Sources & evidence

ORD record
ord-20bebdff021f467d93bb0b1b132a918d
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

Loading…