Chlorotrimethylsilane → (S)-3-{3-Benzyloxy-4-[1,1,4-trioxo-5-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-2-yl]-phenyl}-2-tert-butoxycarbonylaminopropionic Acid Tert-butyl Ester

HRID 660634Notes

Reaction equation

HRID 660634 reaction equation
Cl[Si](C)(C)C.[C:6]([O:10][C:11](=[O:23])[C@@H:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]I)([CH3:9])([CH3:8])[CH3:7].[CH2:24]([O:31][C:32]1[CH:37]=[C:36](I)[CH:35]=[CH:34][C:33]=1[N:39]1[S:43](=[O:45])(=[O:44])[N:42]([CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:41](=[O:52])[CH2:40]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>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].O>[C:6]([O:10][C:11](=[O:23])[C@@H:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][C:36]1[CH:35]=[CH:34][C:33]([N:39]2[CH2:40][C:41](=[O:52])[N:42]([CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[S:43]2(=[O:45])=[O:44])=[C:32]([O:31][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:37]=1)([CH3:9])([CH3:8])[CH3:7]

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 80271Tri-o-tolylphosphineHCID 54762716(R)-2-tert-butoxycarbonylamino-3-iodopropionic acid tert-butyl esterHCID 667569375-(2-Benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one

Product 1

HCID 68840018(S)-3-{3-Benzyloxy-4-[1,1,4-trioxo-5-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-2-yl]-phenyl}-2-tert-butoxycarbonylaminopropionic Acid Tert-butyl Ester

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of zinc powder (645 mg, 9.9 mmol) in DMF (1 mL) under argon is added chlorotrimethylsilane (83 mg, 0.76 mmol) and the mixture is stirred at RT for 30 min. To this is added a solution of (R)-2-tert-butoxycarbonylamino-3-iodopropionic acid tert-butyl ester (1.1 g, 2.96 mmol) in DMF (1.8 mL) dropwise and the mixture is stirred at RT for 30 min. An additional 2.5 mL of DMF is added and any insoluble material is filtered. The filtrate is added to a mixture of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (900 mg, 1.65 mmol), tri-o-tolylphosphine (100 mg, 0.33 mmol) and Pd2(dba)3 (74 mg, 0.08 mmol) and the mixture is stirred at RT for 90 min. Water is added and the mixture is extracted with EtOAc. The organic phase is washed with water (2×) and brine then is dried over sodium sulfate. The solvent is remover under reduced pressure and the residue is purified by flash chromatography using EtOAc/hexane (10%) as eluent to give the title compound as an off-white solid.

Workup

  1. stirringthe mixture is stirred at RT for 30 min
  2. filtrationany insoluble material is filtered
  3. stirringthe mixture is stirred at RT for 90 min
  4. extractionthe mixture is extracted with EtOAc
  5. washThe organic phase is washed with water (2×) and brine
  6. dry with materialthen is dried over sodium sulfate
  7. customthe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-05dd9d8117dc4be4a8c02d3792c3dffd
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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