Epothilone A → Epothilone C

HRID 43242

Reaction equation

HRID 43242 reaction equation
[Mg].[CH3:2][C:3]1[S:7][CH:6]=[C:5](/[CH:8]=[C:9](/[C@H:11]2[O:29][C:27](=[O:28])[CH2:26][C@H:25]([OH:30])[C:24]([CH3:32])([CH3:31])[C:22](=[O:23])[C@H:21]([CH3:33])[C@@H:20]([OH:34])[C@@H:19]([CH3:35])[CH2:18][CH2:17][CH2:16][C@H:14]3O[C@H:13]3[CH2:12]2)\[CH3:10])[N:4]=1>[Cl-].[Cl-].C1([Ti+2]C2C=CC=C2)C=CC=C1.C1COCC1>[CH3:2][C:3]1[S:7][CH:6]=[C:5](/[CH:8]=[C:9](/[C@H:11]2[O:29][C:27](=[O:28])[CH2:26][C@H:25]([OH:30])[C:24]([CH3:32])([CH3:31])[C:22](=[O:23])[C@H:21]([CH3:33])[C@@H:20]([OH:34])[C@@H:19]([CH3:35])[CH2:18][CH2:17][CH2:16][CH:14]=[CH:13][CH2:12]2)\[CH3:10])[N:4]=1

Participants

5

Reactant 2

HCID 448799Epothilone AHCID 5462224Magnesium

Product 1

HCID 9891226Epothilone CYield 80%

Reagents, catalysts & solvents 2

HCID 178420582HCID 178420582, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a two-necked flask was added chopped pieces of magnesium turnings (24 mg, 1.0 mmol). The flask was flame-dried under vacuum and cooled under argon. Bis(cyclopentadienyl)titanium dichloride (250 mg, 1.0 mmol) was added followed by anhydrous THF (5 mL). The stirring suspension was evacuated with low vacuum, and the reaction flask was refilled with argon. The red suspension became dark, turning a homogeneous deep green after 1.5 h with nearly all the magnesium metal being consumed. An aliquot (3.5 mL, 0.70 mmol, 3.5 eq) was removed and cooled to −78° C. under argon. To this solution was added epothilone A (99 mg, 0.20 mmol, 1.0 eq). The reaction mixture was warmed to room temperature and stirred for 15 min. The volatiles were removed in vacuo and the residue was chromatographed two times on silica (25 g), eluting with 35% EtOAc/hexanes to give 76 mg (80%) of epothilone C as a pale yellow viscous oil.

Workup

  1. additionTo a two-necked flask was added
  2. customThe flask was flame-dried under vacuum
  3. temperaturecooled under argon
  4. customThe stirring suspension was evacuated with low vacuum
  5. additionthe reaction flask was refilled with argon
  6. customhomogeneous deep green after 1.5 h
  7. custombeing consumed
  8. customAn aliquot (3.5 mL, 0.70 mmol, 3.5 eq) was removed
  9. temperatureThe reaction mixture was warmed to room temperature
  10. customThe volatiles were removed in vacuo
  11. customthe residue was chromatographed two times on silica (25 g)
  12. washeluting with 35% EtOAc/hexanes

Sources & evidence

ORD record
ord-a6e661f69054463e928515b70525f22a
Source dataset
uspto-grants-2013_09
Patent number
US08536327B2

Linked notes

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