1,4-Dioxane → 1,1-Dimethylethyl {(1S)-2-[4-(bromoacetyl)phenyl]-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate

HRID 1436175Notes

Reaction equation

HRID 1436175 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:10][N:11]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])=[CH:4][CH:3]=1.[Br:30]N1C(=O)CCC1=O.[O:38]1CCO[CH2:40][CH2:39]1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:30][CH2:40][C:39]([C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:10][N:11]2[C:12](=[O:21])[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]2=[O:20])=[CH:4][CH:3]=1)=[O:38]

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 67184N-bromobutanimideHCID 575945641,1-dimethylethyl {(1S)-2-(4-bromophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate

Product 1

HCID 575944941,1-Dimethylethyl {(1S)-2-[4-(bromoacetyl)phenyl]-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamateYield 71%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

A solution of 1,1-dimethylethyl {(1S)-2-(4-bromophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate (21.7 mmol), 1-ethoxyvinyltri-n-butylin (43.5 mmol), and trans-dichlorobis(triphenylphospine)palladium(II) (5 mol %) were stirred in anhydrous dioxane (300 mL) at 100° C. for 3 h. The reaction was then concentrated in vacuo and redissolved in a solution of tetrahydrofuran and water (3:1, 400 mL) and treated with N-bromosuccinimide (108.8 mmol) and stirred at RT for half an hour. The reaction solution was then concentrated to dryness and redissolved in ethyl acetate (150 mL) and precipate formed upon addition of hexanes (350 mL). The precipitate was filtered and dried to afford the title product as yellow solid (71%). ESMS [M+H]+: 502.4.

Workup

  1. concentrationThe reaction was then concentrated in vacuo
  2. dissolutionredissolved in a solution of tetrahydrofuran and water (3:1, 400 mL)
  3. concentrationThe reaction solution was then concentrated to dryness
  4. dissolutionredissolved in ethyl acetate (150 mL)
  5. customprecipate formed upon addition of hexanes (350 mL)
  6. filtrationThe precipitate was filtered
  7. customdried

Sources & evidence

ORD record
ord-4fb345880cf44ded99d13ec8463ec558
Source dataset
uspto-grants-2009_11
Patent number
US07618981B2

Reaction notes

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