Dichloromethane → HCID 68619512, compound

HRID 1433793Notes

Reaction equation

HRID 1433793 reaction equation
[NH2:1][C@:2](C1C=CC(I)=CC=1Cl)([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH2:5])=[O:4].[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23].Cl[CH2:28][Cl:29]>C(N(CC)CC)C.C(OCC)C.ClCCl.[Cu](I)I>[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[C:3]([NH:5][C:8]1[CH:7]=[CH:6][C:2]([C:26]#[C:25][Si:22]([CH3:24])([CH3:23])[CH3:21])=[CH:3][C:28]=1[Cl:29])=[O:4]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 66111TrimethylsilylacetyleneHCID 68619402HCID 68619402, compound

Product 1

HCID 68619512HCID 68619512, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalyst2×HCID 8471TriethylamineSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

To a dry flask were added (S)-2-amino-(2-chloro-4-iodo-phenyl)-3-phenyl-propionamide (980 mg, 2.44 mmol), bis-dichlorotriphenylphosphine palladium (19.8 mg, 0.0489 mmol), and copper iodide (9.5 mg, 0.049 mmol). To this mixture was added trimethylsilylacetylene (269.7 mg, 2.69 mmol) in dry triethylamine (1.46 mL). Dry dichloromethane (1 mL) was added after 30 minutes. After 3 hours additional bis-dichlorotriphenylphosphine palladium (40 mg, 0.099 mmol) and copper iodide (20 mg, 0.099 mmol) were added. After 1 hour the reaction mixture was diluted with a 1:1 v/v mixture of diethyl ether/dichloromethane and passed through a bed of silica gel and the silica gel then eluted with a 2:3 v/v mixture of diethyl ether/dichloromethane. The eluant was concentrated in vacuo and the crude residue was purified by chromatography over silica gel gradient eluted with 5 to 30% v/v diethyl ether in hexanes. The pooled fractions containing product were concentrated to give (S)-2-amino-N-(2-chloro-4-trimethylsilanylethynyl-phenyl)-3-phenyl-propionamide as a white solid (820 mg 90% yield).

Workup

  1. washthe silica gel then eluted with a 2:3 v/v mixture of diethyl ether/dichloromethane
  2. concentrationThe eluant was concentrated in vacuo
  3. customthe crude residue was purified by chromatography over silica gel gradient
  4. washeluted with 5 to 30% v/v diethyl ether in hexanes
  5. additionThe pooled fractions containing product
  6. concentrationwere concentrated

Sources & evidence

ORD record
ord-7bd04771517f45d593b7a75e847bdfaa
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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