Sodium Trifluoroacetate → (2,4-Bis-benzyloxy-5-trifluoromethyl-phenyl)-(1,3-dihydro-isoindol-2-yl)-methanone

HRID 1625360Notes

Reaction equation

HRID 1625360 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12](Br)=[CH:11][C:10]=1[C:24]([N:26]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:35][C:36]([F:41])([F:40])C([O-])=O.[Na+]>[Cu]I>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12]([C:36]([F:41])([F:40])[F:35])=[CH:11][C:10]=1[C:24]([N:26]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 517019Sodium TrifluoroacetateHCID 46915778(2,4-Bis-benzyloxy-5-bromo-phenyl)-(1,3-dihydro-isoindol-2-yl)-methanone

Product 1

HCID 59263097(2,4-Bis-benzyloxy-5-trifluoromethyl-phenyl)-(1,3-dihydro-isoindol-2-yl)-methanoneYield 29.3%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
150 °C

Procedure

A mixture of (2,4-bis-benzyloxy-5-bromo-phenyl)-(1,3-dihydro-isoindol-2-yl)-methanone (491 mg, 0.95 mmol), sodium trifluoroacetate (649 mg, 4.8 mmol) and copper (I) iodide (364 mg, 1.91 mmol) were dried under vacuum (0.04 mbar) for 6 hours. The flask was flushed with nitrogen, DMF (5 mL) was added and the mixture heated at 150° C. for 17 hours. After cooling to r.t., the mixture was diluted with DCM (100 mL) and filtered through Celite, rinsing with DCM. The filtrate was concentrated to dryness and the residue was partially purified by flash chromatography on silica (ethyl acetate/petrol gradient, 0-20%). The purest fraction was recrystallised from methanol to afford the title compound as a white solid (140 mg, 29%). 1H NMR (methanol-d4) 7.60 (1H, s), 7.48-7.44 (2H, m), 7.40 (2H, t), 7.37-7.21 (m, 9H), 7.17 (1H, d), 7.02 (1H, s), 5.29 (2H, s), 5.24 (2H, s), 4.88 (2H, s), 4.62 (2H, s). MS: [M+H]+ 504.

Workup

  1. customwere dried under vacuum (0.04 mbar) for 6 hours
  2. customThe flask was flushed with nitrogen, DMF (5 mL)
  3. additionwas added
  4. temperatureAfter cooling to r.t.
  5. additionthe mixture was diluted with DCM (100 mL)
  6. filtrationfiltered through Celite
  7. washrinsing with DCM
  8. concentrationThe filtrate was concentrated to dryness
  9. customthe residue was partially purified by flash chromatography on silica (ethyl acetate/petrol gradient, 0-20%)
  10. customThe purest fraction was recrystallised from methanol

Sources & evidence

ORD record
ord-087b40b0c7ab480a818f06aec72d0f0b
Source dataset
uspto-grants-2014_07
Patent number
US08779132B2

Reaction notes

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