HCID 131726605, compound → HCID 69391705, compound

HRID 916818Notes

Reaction equation

HRID 916818 reaction equation
ClC1C=CC=C(Cl)C=1COCCOC1C=CC(CCN2C[C@@H](C3C=CC4OC(C)(C)OCC=4C=3)OC2=O)=CC=1.[C:40]([O:43][C:44]1[CH:49]=[CH:48][C:47]([C@@H:50]([OH:74])[CH2:51][NH:52][CH2:53][CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH2:62][CH2:63][O:64][CH2:65][C:66]3[C:71]([Cl:72])=[CH:70][CH:69]=[CH:68][C:67]=3[Cl:73])=[CH:57][CH:56]=2)=[CH:46][C:45]=1[CH2:75][OH:76])(=[O:42])[CH3:41].O([Si](C)(C)C)[K]>C1COCC1>[C:40]([O:43][C:44]1[CH:49]=[CH:48][C:47]([C@@H:50]([OH:74])[CH2:51][NH:52][CH2:53][CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH2:62][CH2:63][O:64][CH2:65][C:66]3[C:67]([Cl:73])=[CH:68][CH:69]=[CH:70][C:71]=3[Cl:72])=[CH:57][CH:56]=2)=[CH:46][C:45]=1[CH2:75][OH:76])(=[O:42])[CH3:41]

Participants

4

Reactant 2

HCID 131726605HCID 131726605, compoundHCID 178504318HCID 178504318, compound

Product 1

HCID 69391705HCID 69391705, compoundYield 146.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

4-((1R)-2-{[2-(4-{2-[(2,6-Dichlorobenzyl)oxy]ethoxy}phenyl)ethyl]amino}-1-hydroxyethyl)-2-(hydroxymethyl)phenol acetate (5R)-3-[2-(4-{2-[(2,6-Dichlorobenzyl)oxy]ethoxy}phenyl)ethyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (160 mg) in THF (4 ml) was treated with KOSiMe3 (179 mg) and the resulting solution was heated at 75° C. for 2 h. The reaction mixture was then quenched with MeOH and concentrated in vacuo. The residue was then diluted in MeOH, and purified on an SCX-2 cartridge (10 g) eluting with EtOH followed by 10% aqueous NH3 in EtOH. The ammonia fractions were then combined and concentrated in vacuo. The residue was dissolved in acetic acid (3 ml) and water (1 ml) and heated at 75° C. for 20 min. The solution was then concentrated in vacuo and azeotroped with MeOH to give the title compound (115 mg). LCMS RT=2.49 min, ES+ve 506 (MH)+

Workup

  1. customThe reaction mixture was then quenched with MeOH
  2. concentrationconcentrated in vacuo
  3. additionThe residue was then diluted in MeOH
  4. custompurified on an SCX-2 cartridge (10 g)
  5. washeluting with EtOH
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in acetic acid (3 ml)
  8. temperaturewater (1 ml) and heated at 75° C. for 20 min
  9. concentrationThe solution was then concentrated in vacuo
  10. customazeotroped with MeOH

Sources & evidence

ORD record
ord-663ecdd07ae146fe9d5706aa10784da6
Source dataset
uspto-grants-2007_09
Patent number
US07271197B2

Reaction notes

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