Tri-o-tolylphosphine → Methanesulfonic acid 2-[3-benzyloxy-4-(5-benzyloxymethyl-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-5-fluorobenzyl]-4-methylphenyl ester

HRID 889246Notes

Reaction equation

HRID 889246 reaction equation
I[CH2:2][C:3]1[CH:8]=[CH:7][C:6](C)=[CH:5][C:4]=1[O:10][S:11]([CH3:14])(=[O:13])=[O:12].[CH3:15]C1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH2:37]([O:44][C:45]1[CH:50]=[C:49](I)[CH:48]=[C:47]([F:52])[C:46]=1[N:53]1[S:57](=[O:59])(=[O:58])[N:56]([CH2:60][O:61][CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[C:55](=[O:69])[CH2:54]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>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]>[CH2:37]([O:44][C:45]1[CH:50]=[C:49]([CH:48]=[C:47]([F:52])[C:46]=1[N:53]1[CH2:54][C:55](=[O:69])[N:56]([CH2:60][O:61][CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[S:57]1(=[O:59])=[O:58])[CH2:2][C:3]1[CH:8]=[C:7]([CH3:15])[CH:6]=[CH:5][C:4]=1[O:10][S:11]([CH3:14])(=[O:12])=[O:13])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 684293105-(2-Benzyloxy-6-fluoro-4-iodophenyl)-2-benzyloxymethyl-1,1-dioxo-1,2,5-thiadiazolidin-3-oneHCID 86638982Methanesulfonic acid 2-iodomethyl-5-methylphenyl ester

Product 1

HCID 86638981Methanesulfonic acid 2-[3-benzyloxy-4-(5-benzyloxymethyl-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-5-fluorobenzyl]-4-methylphenyl ester

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

Zinc dust (200 mg, 3.08 mmol) is added to a flask and heated with a heat gun under high vacuum to remove moisture. DMF (1.0 mL, freshly distilled) is added under argon. 1,2-Dibromoethane (0.02 mL) is added and heated with heat gun until bubbling is observed. After it is cooled to RT, TMSCl (0.02 mL) is added and the mixture is stirred at RT for 20 min. Then a solution of methanesulfonic acid 2-iodomethyl-5-methylphenyl ester (224 mg, 0.688 mmol) in DMF (0.6 mL, freshly distilled) is added and the mixture is heated at 40° C. for 45 min. Then it is cooled to RT. Pd2(dba)3 (20 mg, 0.02 mmol), P(o-tolyl)3 (28.4 mg, 0.10 mmol) is added followed by a solution of 5-(2-benzyloxy-6-fluoro-4-iodophenyl)-2-benzyloxymethyl-1,1-dioxo-1,2,5-thiadiazolidin-3-one (200 mg, 0.344 mmol) in DMF (1.4 mL, freshly distilled). The mixture is stirred at RT for 2 h. ETOAc is added and it is filtered through Celite. The filtrate is then washed with 1N HCl solution, water and brine. It is then dried and concentrated. The residue is purified to give the title compound.

Workup

  1. temperatureheated with a heat gun under high vacuum
  2. customto remove moisture
  3. distillationDMF (1.0 mL, freshly distilled)
  4. additionis added under argon
  5. addition1,2-Dibromoethane (0.02 mL) is added
  6. temperatureheated
  7. temperaturewith heat gun
  8. customuntil bubbling
  9. additionTMSCl (0.02 mL) is added
  10. additionis added
  11. temperaturethe mixture is heated at 40° C. for 45 min
  12. temperatureThen it is cooled to RT
  13. distillationfreshly distilled)
  14. stirringThe mixture is stirred at RT for 2 h
  15. additionETOAc is added
  16. filtrationit is filtered through Celite
  17. washThe filtrate is then washed with 1N HCl solution, water and brine
  18. customIt is then dried
  19. concentrationconcentrated
  20. customThe residue is purified

Sources & evidence

ORD record
ord-e97501bfa6ca478493f47297fe4778cd
Source dataset
uspto-grants-2012_08
Patent number
US08252820B2

Reaction notes

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