Acetyl chloride → Methyl (S)-2-benzyloxycarbonylamino-4-oxopentanoate

HRID 1009312Notes

Reaction equation

HRID 1009312 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:13]I)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrCCBr.Cl[Si](C)(C)C.[C:28](Cl)(=[O:30])[CH3:29]>C1C=CC=CC=1.CN(C)C(=O)C.[Cu].[Zn].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:13][C:28](=[O:30])[CH3:29])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 6367Acetyl chlorideHCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 10915437(R)-2-Benzyloxycarbonylamino-3-iodo-propionic acid methyl ester

Product 1

HCID 13857370Methyl (S)-2-benzyloxycarbonylamino-4-oxopentanoate

Reagents, catalysts & solvents 4

HCID 10290809Zinc copper coupleCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 241BenzeneSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of methyl N-((benzyloxy)carbonyl)-3-iodo-L-alaninate (10 g, 27.5 mmol), from Step 1, zinc-copper couple (3.3 g) in benzene (110 mL) and N,N-dimethylacetamide (7.4 mL) was sonicated in an ultra-sound bath for 2 hours. Over this period, 3 portions of 1,2-dibromoethane (0.24 mL) and chlorotrimethylsilane (0.17 mL) were added. To this mixture was then added bis(triphenylphosphine)palladium chloride (0.958 g, 1.4 mmol) and acetyl chloride (2.5 mL, 35.2 mmol) and the mixture was heated at 70° C. for 2 hours. After cooling to room temperature, the mixture was filtered on celite with ethyl acetate, the organic layer was then washed with a saturated solution of ammonium chloride, brine (2×), dried over magnesium sulfate, filtered and the solvent evaporated under vacuum. The residue was purified by silica gel chromatography using ethyl acetate and hexanes to afford methyl N-((benzyloxy)carbonyl)-4-oxo-L-norvalinate.

Workup

  1. waitOver this period
  2. filtrationthe mixture was filtered on celite with ethyl acetate
  3. washthe organic layer was then washed with a saturated solution of ammonium chloride, brine (2×)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated under vacuum
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fc23110702854a4293733f697ff6d5b8
Source dataset
uspto-grants-2011_07
Patent number
US07973037B2

Reaction notes

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