Chlorotrimethylsilane → 5-[2-Benzyloxy-4-(6-benzyloxypyridin-2-ylmethyl)-phenyl]-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one

HRID 660544

Reaction equation

HRID 660544 reaction equation
BrCCBr.C[Si](Cl)(C)C.[CH2:10]([O:17][C:18]1[CH:23]=[C:22]([CH2:24]I)[CH:21]=[CH:20][C:19]=1[N:26]1[S:30](=[O:32])(=[O:31])[N:29]([CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:28](=[O:39])[CH2:27]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(C2C=CC=CC=2)C=CC=CC=1.[CH2:52]([O:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62](Br)[N:61]=1)[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN(C)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]>[CH2:10]([O:17][C:18]1[CH:23]=[C:22]([CH2:24][C:62]2[CH:63]=[CH:64][CH:65]=[C:60]([O:59][CH2:52][C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)[N:61]=2)[CH:21]=[CH:20][C:19]=1[N:26]1[S:30](=[O:32])(=[O:31])[N:29]([CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:28](=[O:39])[CH2:27]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 7095BiphenylHCID 78391,2-DibromoethaneHCID 8174752-Benzyloxy-6-bromopyridineHCID 667568095-(2-Benzyloxy-4-iodomethylphenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one

Product 1

HCID 688388345-[2-Benzyloxy-4-(6-benzyloxypyridin-2-ylmethyl)-phenyl]-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent3×

Procedure

In a pressure vessel, zinc powder (429 mg, 6.6 mmol) is dried by heating under vacuum, then cooled, placed under N2, and slurried in N,N-dimethylacetamide (0.75 mL). To the slurry is added 1,2-dibromoethane (0.044 mL, 0.51 mmol) and the mixture is heated until boiling. The mixture is allowed to cool, and TMSCl (65 mL, 0.51 mmol) is added, followed by stirring for 30 min to produce a green solution. To the activated zinc is added 5-(2-benzyloxy-4-iodomethylphenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (600 mg, 1.1 mmol) in N,N-dimethylacetamide (1 mL) over 30 min. The organozinc solution is filtered and degassed with N2, then to it is added Pd2(dba)3 (50 mg, 0.055 mmol) and 2-di-t-butylphosphino)biphenyl (66 mg, 0.22 mmol), followed by degassed 2-benzyloxy-6-bromopyridine (350 mg, 1.3 mmol) in N,N-dimethylacetamide. The vessel is sealed and the reaction is stirred at 80° C. for 18 h. The reaction is allowed to cool to RT then is filtered through Celite. The resulting solution is diluted with EtOAc (10 mL) and washed with water and brine, then dried over MgSO4. The solvent is removed under reduced pressure and the crude residue is purified by silica gel chromatography using a gradient of 0-75% EtOAc/hexane to afford the title compound as a colorless oil: (M+H)+=616

Workup

  1. temperatureby heating under vacuum
  2. temperaturecooled
  3. temperaturethe mixture is heated until boiling
  4. temperatureto cool
  5. customto produce a green solution
  6. filtrationThe organozinc solution is filtered
  7. customdegassed with N2
  8. customThe vessel is sealed
  9. stirringthe reaction is stirred at 80° C. for 18 h
  10. filtrationthen is filtered through Celite
  11. additionThe resulting solution is diluted with EtOAc (10 mL)
  12. washwashed with water and brine
  13. dry with materialdried over MgSO4
  14. customThe solvent is removed under reduced pressure
  15. customthe crude residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-846673c26e664899b472e1c0d502d6f6
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Linked notes

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