Iodine → (S)-Methyl 2-(tert-butoxycarbonylamino)-3-(3-oxocyclopent-1-enyl)propanoate

HRID 58831Notes

Reaction equation

HRID 58831 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14]I)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].II.I[C:19]1[CH2:23][CH2:22][C:21](=[O:24])[CH:20]=1.O>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:19]1[CH2:23][CH2:22][C:21](=[O:24])[CH:20]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 807IodineHCID 962WaterHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 109766733-Iodo-2-cyclopenten-1-one

Product 1

HCID 69933833(S)-Methyl 2-(tert-butoxycarbonylamino)-3-(3-oxocyclopent-1-enyl)propanoateYield 60%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 6228DimethylformamideSolvent3×

Procedure

A solution of (R)-methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (32.9 g, 0.100 mol) in DMF (20 mL) was added to a mixture of Zn (19.5 g, 0.300 mol) and iodine (6.6 g, 26 mmol) in DMF (30 mL) under nitrogen protection. The mixture was stirred for 1 h at ambient temperature. Then a solution of 3-iodocyclopent-2-enone (20.8 g, 0.100 mol) in DMF (50 mL), Pd2(dba)3 (2.3 g, 2.5 mmol) and S—Phos (2.1 g, 5.0 mmol) were added successively. The reaction mixture was stirred overnight at 50° C. The mixture was cooled to ambient temperature and water (100 mL) was added. The resulting mixture was extracted with EtOAc (150 mL×3). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=5:1 to 2:1) to afford (S)-methyl 2-(tert-butoxycarbonylamino)-3-(3-oxocyclopent-1-enyl)propanoate (17 g, 60% yield) as a pale yellow oil.

Workup

  1. stirringThe reaction mixture was stirred overnight at 50° C
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionThe resulting mixture was extracted with EtOAc (150 mL×3)
  4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=5:1 to 2:1)

Sources & evidence

ORD record
ord-0e0dea0f11534af2b8d415d69246786e
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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