Dimethyl Sulfide → Epothilone A

HRID 392472

Reaction equation

HRID 392472 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 2 KHSO5.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-0a21c547423249eeab153057c21af7e4
Source dataset
uspto-grants-2004_10
Patent number
US06800653B2

Linked notes

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