Dimethyl Sulfide → Epothilone A

HRID 2184990Notes

Reaction equation

HRID 2184990 reaction equation
[CH3:1][C:2]1[S:6][CH:5]=[C:4](/[CH:7]=[C:8](/[C@H:10]2[O:27][C:25](=[O:26])[CH2:24][C@H:23]([OH:28])[C:22]([CH3:30])([CH3:29])[C:20](=[O:21])[C@H:19]([CH3:31])[C@@H:18]([OH:32])[C@@H:17]([CH3:33])[CH2:16][CH2:15][CH2:14][CH:13]=[CH:12][CH2:11]2)\[CH3:9])[N:3]=1.C(C(C)=[O:39])(F)(F)F.OS([O-])(=O)=O.[K+].C([O-])(O)=O.[Na+].CSC>CC#N.C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=O.[Na+].[Na+].O>[CH3:1][C:2]1[S:6][CH:5]=[C:4](/[CH:7]=[C:8](/[C@H:10]2[O:27][C:25](=[O:26])[CH2:24][C@H:23]([OH:28])[C:22]([CH3:30])([CH3:29])[C:20](=[O:21])[C@H:19]([CH3:31])[C@@H:18]([OH:32])[C@@H:17]([CH3:33])[CH2:16][CH2:15][CH2:14][C@H:13]3[O:39][C@H:12]3[CH2:11]2)\[CH3:9])[N:3]=1

Participants

9

Reactant 5

HCID 1068Dimethyl SulfideHCID 9871Methyl trifluoromethyl ketoneHCID 516892Sodium BicarbonateHCID 516920Potassium bisulfateHCID 9891226Epothilone C

Product 1

HCID 448799Epothilone AYield 57%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8759EDTA disodium saltSolvent

Procedure

To solution of epothilone C (100 mg, 0.21 mmol) in CH3CN (2.5 mL) and 0.0004 M Na2EDTA (1.5 ml) at 0° C. were added excess CF3COCH3 (1 mL) followed by 2KHSO5797. KHSO4.K2SO4 (potassium peroxymonosulfate) (325 mg, 0.53 mmol) and NaHCO3 (75 mg, 0.89 mmol). The reaction mixture was stirred for 35 min then treated with dimethylsulfide (0.50 mL) and water (3.75 mL). The reaction mixture was warmed to room temperature, extracted with EtOAc (4×10 mL), dried over MgSO4, filtered, and concentrated. The residue was chromatographed with 55% EtOAc/hexanes to give epothilone A (59 mg, 57%) and compound A (30 mg, 29%) as a white solid. m/z: 494(M+H)+.

Workup

  1. extractionextracted with EtOAc (4×10 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed with 55% EtOAc/hexanes

Sources & evidence

ORD record
ord-3f435754458c4598ad148fe61d53acb7
Source dataset
uspto-grants-2002_06
Patent number
US06399638B1

Reaction notes

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