Iodine → HCID 90456722, compound

HRID 625872Notes

Reaction equation

HRID 625872 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.Br[C:48]1[CH:49]=[C:50]([Cl:56])[C:51]([F:55])=[C:52]([Cl:54])[CH:53]=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:48]3[CH:53]=[C:52]([Cl:54])[C:51]([F:55])=[C:50]([Cl:56])[CH:49]=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:48]1[CH:53]=[C:52]([Cl:54])[C:51]([F:55])=[C:50]([Cl:56])[CH:49]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

10

Reactant 4

HCID 807Iodine2×HCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 229262305-Bromo-1,3-dichloro-2-fluorobenzene

Product 2

HCID 90456722HCID 90456722, compoundHCID 90456910HCID 90456910, 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), 5-bromo-1,3-dichloro-2-fluorobenzene (556 mg, 2.279 mmol) and the reaction mixture was allowed to stir at rt for 16 h. The crude mixture was diluted in 30 mL of EtOAc and DMF was removed using four aqueous washes. The organic phase was dried over anhydrous sodium sulfate. The solution was filtered and concentrated and the crude product 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-dichloro-4-fluorophenyl)propanoate, 0.102 g which was taken into next step directly.

Workup

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

Sources & evidence

ORD record
ord-564cd7e2d0624118a904646381e4cfdd
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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