Water → 2-Bromo-1-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-ethanone

HRID 2038955Notes

Reaction equation

HRID 2038955 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[CH:12]=[CH:13][C:14]([Br:16])=[CH:15][C:10]=3[CH2:9][O:8][CH2:7][C:6]=2[CH:17]=1.C([Sn](CCCC)(CCCC)[CH:23]=[CH:24][O:25]CC)CCC.O.C1C(=O)N([Br:44])C(=O)C1>O1CCOCC1.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:44][CH2:23][C:24]([C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[CH:12]=[CH:13][C:14]([Br:16])=[CH:15][C:10]=3[CH2:9][O:8][CH2:7][C:6]=2[CH:17]=1)=[O:25]

Participants

7

Reactant 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)etheneHCID 223161653,9-Dibromo-5,7-dihydrodibenzo[c,e]oxepine

Product 1

HCID 596102962-Bromo-1-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-ethanoneYield 25.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of 3,9-dibromo-5,7-dihydro-dibenzo[c,e]oxepine (416 mg, 1.2 mmol) and tributyl(ethoxyvinyl)stannane (878 μl, 2.6 mmol) in dioxane (6 ml) was added PdCl2(PPh3)2 (30 mg). The mixture was heated at 80° C. for 16 hours and was cooled to 0° C. Water (2 ml) was added, followed by slow addition of NBS (464 mg, 2.6 mmol) over 5 minutes period. The mixture was stirred at 0° C. for additional 40 minutes, and the solvent was removed under reduced pressure. The mixture was diluted with EtOAc, and was washed with water and brine and dried with sodium sulfate. Concentration and purification by flash column chromatography (hexane/EtOAc) gave 2-bromo-1-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-ethanone (120 mg). Pyrrolidine-1,2-dicarboxylic acid 2-[2-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-2-oxo-ethyl]ester 1-tert-butyl ester: To the solution of (S)-Boc-Pro-OH (118 mg, 0.55 mmol) and triethylamine (65 μl, 0.46 mmol) in acetonitrile (2 ml) was added a solution of 2-bromo-1-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-ethanone (120 mg, 0.31 mmol) in DMF (4 ml). The mixture was stirred for 10 hours, and the solvent was evaporated. The mixture was diluted with EtOAc, and washed with water and brine, and was dried with sodium sulfate. Concentration gave pyrrolidine-1,2-dicarboxylic acid 24-[2-(9-bromo-5,7-dihydro-dibenzo[c,e]oxepin-3-yl)-2-oxo-ethyl]ester 1-tert-butyl ester (160 mg). m/z: 553.8 (M+Na)+.

Workup

  1. temperaturewas cooled to 0° C
  2. customthe solvent was removed under reduced pressure
  3. additionThe mixture was diluted with EtOAc
  4. washwas washed with water and brine
  5. dry with materialdried with sodium sulfate
  6. concentrationConcentration and purification by flash column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-37cf1a26046449f1b633875b4f332dfc
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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