N-bromobutanimide → (2S)-2-(1-(4-bromophenyl)-3-ethoxy-1,3-dioxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylate

HRID 1873901

Reaction equation

HRID 1873901 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C1C(=O)N(Br)C(=O)C1.BrC(C(C1C=CC(Br)=CC=1)=O)C(OCC)=O.[C:40]([N:47]1[CH2:54][CH2:53][CH2:52][C@H:48]1[C:49]([OH:51])=[O:50])([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CCN(C(C)C)C(C)C>C(Cl)Cl.C(#N)C>[N:47]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:54][CH2:53][CH2:52][CH:48]1[C:49]([O:51][C@H:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)=[O:15])=[O:50]

Participants

8

Reactant 5

HCID 67184N-bromobutanimideHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2757149Ethyl 3-(4-bromophenyl)-3-oxopropanoateHCID 13048362Ethyl 2-bromo-3-(4-bromophenyl)-3-oxopropanoate

Product 1

HCID 66769804(2S)-2-(1-(4-bromophenyl)-3-ethoxy-1,3-dioxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The ethyl 3-(4-bromophenyl)-3-oxopropanoate (15 g, 55 mmol) was dissolved in CH2Cl2 (600 mL) and freshly recrystallized NBS (9.8 g, 55 mmol) was added and the solution stirred 18 hr. The reaction mixture was washed with NaHCO3 solution, brine, and dried (MgSO4), filtered, and concentrated to give a residue which was not purified. Ethyl 2-bromo-3-(4-bromophenyl)-3-oxopropanoate (16.5 g, 48 mmol) and N-Boc-L-proline (10 g, 48 mmol) were taken up in acetonitrile (450 mL) and Hunig's base (16 mL, 95 mmol) was added and the solution stirred 18 hr. The solvent was removed by rotary evaporation and the residue taken up in ethyl acetate, washed with 0.1 N HCl, and brine. 1H NMR (300 MHz, DMSO-d6) δ 7.95 (d, J=8.4 Hz, 2H), 7.79 (d, J=8.4 Hz, 2H), 6.68-6.65 (m, 1H), 4.39-4.30 (m, 1H), 4.21-4.12 (m, 2H), 2.27-2.21 (m, 1H), 2.0-1.95 (m, 1H), 1.90-1.76 (m, 2H), 1.39 (s, 2H), 1.31 (s, 9H), 1.11 (t, J=7.3 Hz, 3H).

Workup

  1. washThe reaction mixture was washed with NaHCO3 solution, brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. customwas not purified
  7. stirringthe solution stirred 18 hr
  8. customThe solvent was removed by rotary evaporation
  9. washwashed with 0.1 N HCl, and brine

Sources & evidence

ORD record
ord-46c30ec7cdfb468daf2fa733bc0314af
Source dataset
uspto-grants-2012_11
Patent number
US08303944B2

Linked notes

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