1-Bromo-3-fluorobenzene → 3,4-Dimethyl-1-[(E)-3-(3-fluorophenyl)prop-2-enoyl]-5-phenylimidazolidin-2-one

HRID 1816003Notes

Reaction equation

HRID 1816003 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.[C:9]([N:13]1[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]([CH3:24])[N:15]([CH3:25])[C:14]1=[O:26])(=[O:12])[CH:10]=[CH2:11].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:25][N:15]1[CH:16]([CH3:24])[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:13]([C:9](=[O:12])/[CH:10]=[CH:11]/[C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=2)[C:14]1=[O:26]

Participants

7

Reactant 4

HCID 140821-Bromo-3-fluorobenzeneHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 228977581-Acryloyl-3,4-dimethyl-5-phenylimidazolidin-2-one

Product 1

HCID 698141353,4-Dimethyl-1-[(E)-3-(3-fluorophenyl)prop-2-enoyl]-5-phenylimidazolidin-2-oneYield 76%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 1-bromo-3-fluorobenzene (525 mg, 3 mmole), (4 R, 5 S)-1-acryloyl-3,4-dimethyl-5-phenylimidazolidin-2-one (500 mg, 2 mmole), Pd(OAc)2 (22 mg, 0.10 mmole), P(o-tolyl)3 (61 mg, 0.20 mmole), and (i-Pr)2NEt (0.73 mL, 4.2 mmole) in dry DMF (10 mL) was degassed (3×vacuum/N2 purge) then heated to 110° C. After 2 hr the mixture was cooled and poured into EtOAc. The resulting mixture was washed with H2O (3×), and the combined aqueous layers were back-extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered through a plug of silica gel, and concentrated. The residue was taken up in 1:1 Et2O/hexanes (10 mL) and cooled at −20° C. overnight. The solid was collected and dried in vacuo to afford the title compound (514 mg, 76%): 1H NMR (300 MHz, CDCl3) δ 8.18 (d, J=15.9 Hz, 1 H), 7.64 (d, J=15.9 Hz, 1 H), 7.15-7.45 (m, 8 H), 6.98-7.10 (m, 1 H), 5.42 (d, J=8.5 Hz, 1 H), 3.88-4.03 (m, 1 H), 2.88 (s, 3 H), 0.85 (d, J=6.6 Hz, 3 H); MS (ES) m/e 339 (M+H)+.

Workup

  1. custom(3×vacuum/N2 purge)
  2. temperatureAfter 2 hr the mixture was cooled
  3. additionpoured into EtOAc
  4. washThe resulting mixture was washed with H2O (3×)
  5. extractionthe combined aqueous layers were back-extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered through a plug of silica gel
  8. concentrationconcentrated
  9. temperaturecooled at −20° C. overnight
  10. customThe solid was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-59cac185c99843ed8d224152aaa8db55
Source dataset
uspto-grants-2005_04
Patent number
US06881736B1

Reaction notes

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