Iodine → HCID 86689688, compound

HRID 1623018Notes

Reaction equation

HRID 1623018 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].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:27](C3C=CC(OCCCCCCC)=CC=3)=[CH:28][N:29]=2)=[CH:21][CH:20]=1.C1(P(C2CCCCC2)C2C=CC=CC=2[C:65]2[C:70]([O:71][CH3:72])=[CH:69][CH:68]=[CH:67][C:66]=2OC)CCCCC1>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:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[N:26]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:49])[CH3:50])[CH:27]=[C:28]([C:67]3[CH:66]=[CH:65][C:70]([O:71][CH2:72][CH2:23][CH2:24][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:69][CH:68]=3)[N:29]=2)=[CH:23][CH:24]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

8

Reactant 4

HCID 807Iodine2×HCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86689689HCID 86689689, compound

Product 1

HCID 86689688HCID 86689688, compoundYield 413%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A stirred suspension of zinc (68 mg, 1.03 mmol) in DMF (2 mL) was treated with I2 (12 mg, 0.05 mmol). After the color disappeared, ((R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (110 mg, 0.34 mmol) and further I2 (12 mg, 0.05 mmol) were added. After 30 min, the mixture was de-gassed then 2-(4-bromophenyl)-5-(4-(heptyloxy)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (170 mg, 0.31 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (7 mg, 0.02 mmol) and Pd2(dba)3 (8 mg, 7.8 μmol) were added. After further de-gassing, DMF (2 mL) was added and the reaction mixture was heated at 50° C. overnight. The reaction mixture purified by column chromatography (EA/hexane) to provide 55 mg (25%) of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4-(4-(heptyloxy)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)propanoate as a colorless oil. LCMS-ESI (m/z) calculated for C37H55N3O6Si: 665.9; found 666.4 [M+H]+, tR=3.10 min (Method 8).

Workup

  1. customthe mixture was de-gassed
  2. customAfter further de-gassing
  3. additionDMF (2 mL) was added
  4. customThe reaction mixture purified by column chromatography (EA/hexane)

Sources & evidence

ORD record
ord-94da2f627095492bb1caf1e64353e803
Source dataset
uspto-grants-2014_07
Patent number
US08778923B2

Reaction notes

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