Sodium Thiosulfate → HCID 42637935, compound

HRID 1968909Notes

Reaction equation

HRID 1968909 reaction equation
[CH2:1]([C@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:46])[CH3:45])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:9][C@H:10]([OH:29])[C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)[P:54]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)[O:55][CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)C.N1C=NN=N1.ClC1C=CC=C(C(OO)=[O:86])C=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.ClCCl>[CH2:1]([C@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:45])[CH3:46])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:9][C@H:10]([O:29][P:54]([O:55][CH2:56][C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)([O:63][CH2:64][C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1)=[O:86])[C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 392622RitonavirHCID 5066231Dibenzyl diethylphosphoramiditeHCID 178418441HCID 178418441, compound

Product 1

HCID 42637935HCID 42637935, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of the compound of Example 1 (6.0 g, 8.32 mmol), dibenzyl diethylphosphoramidite (3.96 g), and 1H-tetrazole (2.63 g) in THF (100 mL) was stirred at room temperature for 4 hours. The mixture was cooled to −45° C., followed by dropwise addition of a solution of m-chlorperbenzoic acid (7.2 g) in dichloromethane (100 mL). The mixture was warmed to room temperature and stirred for 1 hour. A 10% solution of Na2S2O3 (100 mL) was added and the mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate and washed with 10% Na2S2O3 and saturated NaHCO3. The organic phase was dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel, eluting with 2% methanol in dichloromethane containing 0.05% NH4OH, to give the title compound (6.2 g, 76% yield).

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. stirringthe mixture was stirred for 30 minutes
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washwashed with 10% Na2S2O3 and saturated NaHCO3
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed on silica gel
  9. washeluting with 2% methanol in dichloromethane containing 0.05% NH4OH

Sources & evidence

ORD record
ord-71ca6161c88640ccad016cb5065287b9
Source dataset
uspto-grants-2013_04
Patent number
US08426388B2

Reaction notes

Loading…