Nitrogen → Cyclopentyl(2S,4E)-5-(4-bromophenyl)-2-[(tert-butoxycarbonyl)amino]pent-4-enoate

HRID 425025Notes

Reaction equation

HRID 425025 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18][CH:19]=[CH2:20])[C:10]([O:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+].N#N>CCCC[N+](CCCC)(CCCC)CCCC.[I-].C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:20]=[CH:19]/[CH2:18][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:10]([O:12][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)=[O:11])=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 115221-Bromo-4-iodobenzeneHCID 516892Sodium Bicarbonate2×HCID 58150165cyclopentyl(2S)-2-[(tert-butoxycarbonyl)amino]pent-4-enoate

Product 1

HCID 59243607Cyclopentyl(2S,4E)-5-(4-bromophenyl)-2-[(tert-butoxycarbonyl)amino]pent-4-enoateYield 52.5%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalyst2×HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A solution of cyclopentyl(2S)-2-[(tert-butoxycarbonyl)amino]pent-4-enoate (0.88 g, 3.11 mmol), 1-bromo-4-iodobenzene (0.966 g, 3.42 mmol), TBAI (1.262 g, 3.42 mmol) and NaHCO3 (0.783 g, 9.32 mmol) in acetonitrile (10 ml) was purged with N2 and palladium acetate (0.070 g, 0.311 mmol) was added. The reaction was then heated at 70° C. overnight. LCMS showed incomplete conversion and so the reaction was purged with nitrogen again and a further 0.05 eq (35 mg) of Pd(OAc)2, 0.25 eq (460 mg) of TBAI and 0.25 eq of NaHCO3 (65 mg) was added and stirred for another 24 hr at 70° C. After cooling to room temperature, the solvent was removed under reduced pressure. The crude residue was absorbed onto silica and purified by column chromatography eluting with 10% EtOAc in iso-hexane. Yield=715 mg, 1.631 mmol, 52.5% yield. LCMS purity>90%: m/z 438 and 440 [M+H]+.

Workup

  1. additionwas added
  2. customso the reaction was purged with nitrogen again
  3. temperatureAfter cooling to room temperature
  4. customthe solvent was removed under reduced pressure
  5. customThe crude residue was absorbed onto silica
  6. custompurified by column chromatography
  7. washeluting with 10% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-9caaac9b2194498aa51c88deafa4e58e
Source dataset
uspto-grants-2012_01
Patent number
US08106091B2

Reaction notes

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