Iodine → Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate

HRID 2408942Notes

Reaction equation

HRID 2408942 reaction equation
II.[CH3:3][O:4][C:5](=[O:17])[C@H:6]([NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][I:8].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.BrC1CCCC=1>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].C(Cl)Cl>[CH3:3][O:4][C:5](=[O:17])[CH:6]([NH:9][C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:7][I:8]

Participants

9

Reactant 4

HCID 807Iodine2×HCID 109646601-bromocyclopenteneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 11416215(S)-Methyl 2-Boc-amino-3-iodopropionate

Product 1

HCID 5051066Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoateYield 30%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a three necked flask charged with zinc dust (2.23 g, 34.1 mmol) under an N2 atmosphere DMF (13 mL) was added. The suspension was efficiently stirred and I2 (0.20 g, 0.80 mmol) was added. ((S)-2-[(tert-Butoxycarbonyl)amino]-3-iodopropionic acid methyl ester (4.50 g, 13.7 mmol) was added in one portion, and immediately after more I2 (0.20 g, 0.80 mmol) and the stirring was continued for 2 h. Negishi coupling was then effected by addition in direct sequence of: Pd2 dba3 (315 mg, 0.34 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (279 mg, 0.68 mmol), and 1-bromocyclopentene (2.32 g, 15.8 mmol) in DMF (4 mL). The reaction was stirred over night. DCM (25 mL) was added and the mixture was filtered, the solids were washed with further DCM, water (30 mL) was added and the phases were separated. The aqueous phase was extracted with DCM (2×20 mL) and the combined organic phases were washed with H2O (20 mL), dried MgSO4, filtered and evaporated. The residue was purified by gradient silica gel chromatography (4-16% EtOAc in iso-hexane) which gave the title compound 1.24 g (30%). GC-MS EI m/z 213 (w), 196 (w), 152, 88, 57, 41.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred over night
  3. filtrationthe mixture was filtered
  4. washthe solids were washed with further DCM, water (30 mL)
  5. additionwas added
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with DCM (2×20 mL)
  8. washthe combined organic phases were washed with H2O (20 mL), dried MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by gradient silica gel chromatography (4-16% EtOAc in iso-hexane) which

Sources & evidence

ORD record
ord-1178c3e4b5f640458f74fddce870fbbc
Source dataset
uspto-grants-2014_08
Patent number
US08815809B2

Reaction notes

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