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 222883Notes

Reaction equation

HRID 222883 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). The mixture was 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). Precipitate formed upon addition of hexanes (350 mL) and 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. customPrecipitate formed upon addition of hexanes (350 mL)
  6. filtrationwas filtered
  7. customdried

Sources & evidence

ORD record
ord-cbb684f3b40c47e492808208d6a3482c
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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