N-bromobutanimide → Pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester

HRID 1185810Notes

Reaction equation

HRID 1185810 reaction equation
[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][C:9](Br)=[CH:10][CH:11]=3)[CH2:6][CH2:5][C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:22]([O:24]CC)=[CH2:23])CCC.C1C(=O)N(Br)C(=O)C1.[C:43]([O:47][C:48]([N:50]1[CH2:54][CH2:53][CH2:52][CH:51]1[C:55]([OH:57])=[O:56])=[O:49])([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C>O1CCOCC1.C(OCC)(=O)C.C(#N)C.O>[C:43]([O:47][C:48]([N:50]1[CH2:54][CH2:53][CH2:52][CH:51]1[C:55]([O:57][CH2:23][C:22]([C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[C:4](=[CH:3][C:2]([Br:1])=[CH:15][CH:14]=3)[CH2:5][CH2:6][C:7]=2[CH:8]=1)=[O:24])=[O:56])=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

10

Reactant 5

HCID 67184N-bromobutanimideHCID 81531DiisopropylethylamineHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 28250532,7-Dibromo-9,10-dihydrophenanthrene

Product 1

HCID 66620898Pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd(Ph3)4 (347 mg, 0.3 mmol) and PdCl2(Ph3)2 (210 mg, 0.3 mmol) were added to a mixture 2,7-dibromo-9,10-dihydro-phenanthrene (2.5 g, 7.4 mmol) and tributyl(1-ethoxyvinyl)tin (2.5 mL, 7.4 mL) in 70 mL dioxane. The reaction mixture was flushed with nitrogen, heated at 80° C. for 16 hours, then cooled to ambient temperature. Water (20 mL) and NBS (1.39 g, 7.8 mmol) were added and the mixture was stirred at room temperature for 40 minutes, then diluted with ethyl acetate (300 mL). Washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was suspended in acetonitrile (70 mL). To it was added a solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (3.2 g, 14.9 mmol) and DIPEA (2.4 mL, 14.1 mmol) in 20 mL acetonitrile. The mixture was stirred at room temperature for 16 hours, then diluted with ethyl acetate (300 mL). The organic layer was washed with NaHCO3 solution and water, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester as a white solid (1.76 g, 46% over two steps). m/z 514.2, 516.2 (M+H)+.

Workup

  1. customThe reaction mixture was flushed with nitrogen
  2. temperaturecooled to ambient temperature
  3. washWashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. stirringThe mixture was stirred at room temperature for 16 hours
  8. washThe organic layer was washed with NaHCO3 solution and water
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe obtained residue was purified by flash chromatography

Sources & evidence

ORD record
ord-077a5d2750024d19810effd9d6636238
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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