Chlorotrimethylsilane → HCID 66996988, compound

HRID 537409Notes

Reaction equation

HRID 537409 reaction equation
BrCCBr.C[Si](Cl)(C)C.C[O:11][C:12](=[O:25])[CH:13]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:15]I.I[C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[C:30]#[N:31].[OH-].[Na+].OS([O-])(=O)=O.[Na+]>CO.C1COCC1.[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.[Pd].CCOC(C)=O.CN(C=O)C>[C:21]([O:20][C:18]([NH:17][CH:13]([CH2:14][CH2:15][C:27]1[CH:34]=[CH:33][CH:32]=[C:29]([C:30]#[N:31])[CH:28]=1)[C:12]([OH:11])=[O:25])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

12

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 14798Sodium HydroxideHCID 1443413-IodobenzonitrileHCID 516919Sodium BisulfateHCID 14394149219752-75-7

Product 1

HCID 66996988HCID 66996988, compoundYield 96%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To 0.39 g (6.0 mmol) of Zn powder under Ar2 is added 0.5 mL of DMF and then 26 μL (0.3 mmol) of 1,2-dibromoethane. After stirring at 60° C. for 30 minutes, the mixture is cooled and 7.6 μL (0.06 mmol) of TMSCl is added. After stirring for 30 minutes, 0.34 g (1.0 mmol) of 4-iodo-2-tert-butoxycarbonylamino-butyric acid methyl ester is added and the mixture is stirred at 35° C. for 30 minutes. The mixture is cooled to rt, and 23 mg (0.040 mmol) of Pd(dba)2, 24 mg (0.080 mmol) of (o-tolyl)3P, and then 0.22 mg (0.95 mmol) 3-iodobenzonitrile are added. After stirring at rt for 3 h, EtOAc is added and the mixture is washed with saturated NH4Cl and brine. The extract is concentrated and purified by preparative HPLC to provide 0.14 g (44%) of Boc-(3-cyano)homophenylalanine-OMe. To 0.12 g (0.38 mmol) of this material in 1 mL of 1:1 MeOH/THF is added 0.38 mL (0.75 mmol) of 2 M NaOH. After stirring for 1 h, 1 M NaHSO4 is added, and the mixture is extracted with EtOAc. The extract is washed with brine, dried over Na2SO4, filtered, and concentrated to provide 0.11 g (96%) of 2-[(tert-butoxycarbonyl)amino]-4-(3-cyanophenyl)butanoic acid.

Workup

  1. temperaturethe mixture is cooled
  2. stirringAfter stirring for 30 minutes
  3. stirringthe mixture is stirred at 35° C. for 30 minutes
  4. temperatureThe mixture is cooled to rt
  5. stirringAfter stirring at rt for 3 h
  6. washthe mixture is washed with saturated NH4Cl and brine
  7. concentrationThe extract is concentrated
  8. custompurified by preparative HPLC
  9. customto provide 0.14 g (44%) of Boc-(3-cyano)homophenylalanine-OMe
  10. stirringAfter stirring for 1 h
  11. extractionthe mixture is extracted with EtOAc
  12. washThe extract is washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-c89b0cc3f76842aba9665a1935848ea8
Source dataset
uspto-grants-2014_10
Patent number
US08859814B2

Reaction notes

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