Iodine → HCID 71304333, compound

HRID 625871Notes

Reaction equation

HRID 625871 reaction equation
II.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16]I)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].C1(P(C2CCCCC2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[C:36](OC)=[CH:35][CH:34]=[CH:33][C:32]=2OC)CCCCC1.[Cl:47][C:48]1[CH:53]=[C:52](I)[CH:51]=[C:50]([Cl:55])[CH:49]=1>CCOC(C)=O.[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].CN(C=O)C>[CH:33]1[C:32]2[CH:6]([CH2:3][O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:52]3[CH:53]=[C:48]([Cl:47])[CH:49]=[C:50]([Cl:55])[CH:51]=3)[C:12]([OH:14])=[O:13])=[O:9])[C:25]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:31]=2[CH:36]=[CH:35][CH:34]=1.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:52]1[CH:53]=[C:48]([Cl:47])[CH:49]=[C:50]([Cl:55])[CH:51]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

10

Reactant 4

HCID 807Iodine2×HCID 764241,3-Dichloro-5-iodobenzeneHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 2

HCID 71304333HCID 71304333, compoundHCID 90456949HCID 90456949, compound

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an oven dried 8 mL vial with teflon cap purged with N2 was added Zinc dust (298 mg, 4.56 mmol), DMF (1.5 mL), and iodine (57.8 mg, 0.228 mmol). To this mixture was added (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (500 mg, 1.519 mmol), immediately followed by iodine (57.8 mg, 0.228 mmol). Pd2(dba)3 (69.6 mg, 0.076 mmol), 2-DICYCLOHEXYLPHOSPHINO-2′,6′-DIMETHOXYBIPHENYL (62.4 mg, 0.152 mmol), 1,3-dichloro-5-iodobenzene (622 mg, 2.279 mmol) and the reaction mixture was allowed to stir at rt for 16 h. The crude mixture was diluted in EtOAc (30 mL) and DMF was removed with four aqueous washes. The organic phase was dried over anhydrous sodium sulfate. The solution was filtered and concentrated, and the crude was purified by silica gel chromatography using 100% hexanes to 30% EtOAc/Hexanes. The desired product was obtained as a pale yellow oil, (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-dichlorophenyl)propanoate, 0.160 g yield in 77% purity by LCMS analysis. Analysis LCMS condition F: Retention time=2.84 min; ESI-MS(+) m/z 348.1 (M+H).

Workup

  1. dry with materialTo an oven dried 8 mL vial with teflon
  2. customcap
  3. custompurged with N2
  4. customDMF was removed with four aqueous washes
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationThe solution was filtered
  7. concentrationconcentrated
  8. customthe crude was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e3b4988bce38445da61dcd3bc8d88807
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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