Dichloromethane methanol → HCID 90067176, compound

HRID 929151Notes

Reaction equation

HRID 929151 reaction equation
I([O-])(=O)(=O)=O.[Na+].[CH2:7]([O:10][C@@H:11]1[CH2:15][O:14][C@@H:13]2[C@H:16]([O:19][C:20]3[N:21]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:22]4[C:23]([N:41]=3)=[N:24][C:25]([C:29]3[CH:34]=[CH:33][C:32]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:31][CH:30]=3)=[C:26]([Cl:28])[CH:27]=4)[CH2:17][O:18][C@H:12]12)[CH:8]=C.C[OH:51].C(Cl)Cl>C(#N)C.O.CCOC(C)=O.O.[Ru](Cl)(Cl)Cl>[Cl:28][C:26]1[CH:27]=[C:22]2[N:21]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:48])([CH3:47])[CH3:49])[C:20]([O:19][C@H:16]3[C@H:13]4[O:14][CH2:15][C@@H:11]([O:10][CH2:7][CH:8]=[O:51])[C@H:12]4[O:18][CH2:17]3)=[N:41][C:23]2=[N:24][C:25]=1[C:29]1[CH:30]=[CH:31][C:32]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[CH:33][CH:34]=1

Participants

8

Reactant 3

HCID 21226129Dichloromethane methanolHCID 23667635Sodium periodate2×HCID 90067174HCID 90067174, compound

Product 1

HCID 90067176HCID 90067176, compound

Reagents, catalysts & solvents 4

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium periodate (53.4 mg, 0.250 mmol) was added to a stirred suspension of 2-[[2-[[(3R,3aR,6R,6aR)-3-allyloxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-5-(4-phenylphenyl)imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane (68.9 mg, 0.111 mmol) and ruthenium(III) chloride hydrate (1.9 mg, 8.43 μmol) in acetonitrile (0.95 ml) and water (0.16 ml). The reaction mixture was stirred at room temperature for 4 h. Additional sodium periodate (31.8 mg, 0.149 mmol) was added and the reaction mixture was stirred for 2 h at room temperature, then in the refrigerator overnight. The reaction mixture was allowed to warm to room temperature before being partitioned between EtOAc (40 ml) and saturated aqueous sodium thiosulfate (30 ml). An inseparable emulsion formed, which was filtered through a pad of Celite™. The biphasic filtrate was re-partitioned and the aqueous layer was extracted with EtOAc (2×20 ml). The organic layers were combined, washed with brine (1×15 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a colorless residue. The residue was dissolved in EtOAc and loaded onto two 500 micron 20 cm×20 cm silica gel plates, which were developed using 10% MeOH/DCM. The silica containing the desired product band was collected and eluted with 10% MeOH/DCM (80 ml). The solvent was evaporated under reduced pressure and the resulting residue was lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C32H36ClN3O6Si 621.21 observed m/e: 622.31 (M+H)+ (Rt 1.34/2 min)

Workup

  1. stirringthe reaction mixture was stirred for 2 h at room temperature
  2. customin the refrigerator overnight
  3. temperatureto warm to room temperature
  4. custombefore being partitioned between EtOAc (40 ml) and saturated aqueous sodium thiosulfate (30 ml)
  5. customAn inseparable emulsion formed
  6. filtrationwhich was filtered through a pad of Celite™
  7. customThe biphasic filtrate was re-partitioned
  8. extractionthe aqueous layer was extracted with EtOAc (2×20 ml)
  9. washwashed with brine (1×15 ml)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. customto give a colorless residue
  14. customThe silica containing the desired product band was collected
  15. washeluted with 10% MeOH/DCM (80 ml)
  16. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bd01e9ec96ac48bd880e2bd378a31b7e
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…