Benzene → 2-(4-Cyano-1-naphthalenyl)-N-(4-fluorophenyl)octahydro-7-methyl 1,3-dioxo-4,7-epoxy-4H-isoindole-4-acetamide

HRID 966889Notes

Reaction equation

HRID 966889 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[CH2:10][C:11]2[O:12][C:13]([CH3:16])=[CH:14][CH:15]=2)=[CH:4][CH:3]=1.[O:18]=[C:19]1[CH:23]=[CH:22][C:21](=[O:24])[N:20]1[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([C:33](F)(F)F)[CH:26]=1.[CH:37]1[CH:42]=CC=C[CH:38]=1>>[C:29]([C:28]1[C:27]2[C:26](=[CH:38][CH:37]=[CH:42][CH:33]=2)[C:25]([N:20]2[C:21](=[O:24])[CH:22]3[CH:23]([C:13]4([CH3:16])[O:12][C:11]3([CH2:10][C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[O:17])[CH2:15][CH2:14]4)[C:19]2=[O:18])=[CH:32][CH:31]=1)#[N:30]

Participants

4

Reactant 3

HCID 241BenzeneHCID 218749284-(2,5-Dioxo-2,5-dihydro-1h-pyrrol-1-yl)-2-(trifluoromethyl)benzonitrileHCID 21874934N-(4-Fluorophenyl)-5-methyl-2-furanacetamide

Product 1

HCID 222925972-(4-Cyano-1-naphthalenyl)-N-(4-fluorophenyl)octahydro-7-methyl 1,3-dioxo-4,7-epoxy-4H-isoindole-4-acetamideYield 54%

Conditions

Temperature
60 °C

Procedure

Compound 216A (0.200 g, 0.858 mmol) and 4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-2-trifluoromethylbenzonitrile (0.164 g, 0.616 mmol) were dissolved in benzene and heated at 60° C. for 14 h. The reaction was then cooled and concentrated in vacuo. The resulting orange oil was dissolved in EtOAc (15 mL) and 10% Pd/C (0.050 g) was added. Hydrogen was then introduced via a balloon. After 3 h, the reaction was filtered through Celite rinsing with EtOAc and concentrated in vacuo. The resulting crude material was purified by preparative TLC on silica eluting with 5% acetone in methylene chloride to give 0.166 g (54%) of compound 216B as a white solid. NMR spectroscopy showed only a single isomer which was determined to be exo by NOE experiments. HPLC: 95% at 3.200 min (retention time) (YMC S5 ODS column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 484.0 [M+H]+.

Workup

  1. temperatureThe reaction was then cooled
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting orange oil was dissolved in EtOAc (15 mL)
  4. addition10% Pd/C (0.050 g) was added
  5. additionHydrogen was then introduced via a balloon
  6. filtrationthe reaction was filtered through Celite
  7. washrinsing with EtOAc
  8. concentrationconcentrated in vacuo
  9. customThe resulting crude material was purified by preparative TLC on silica eluting with 5% acetone in methylene chloride

Sources & evidence

ORD record
ord-3b0dde7ee1394eb3bed2954482204e51
Source dataset
uspto-grants-2005_10
Patent number
US06953679B2

Reaction notes

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