Toluene → Lovastatin

HRID 1603411Notes

Reaction equation

HRID 1603411 reaction equation
[CH3:1][CH2:2][C@@H:3]([C:5]([O:7][C@@H:8]1[C@@H:13]2[C@@H:14]([CH2:19][CH2:20][C@@H:21](O)[CH2:22][C@@H:23]([OH:28])[CH2:24][C:25]([OH:27])=[O:26])[C@@H:15]([CH3:18])[CH:16]=[CH:17][C:12]2=[CH:11][C@H:10]([CH3:30])[CH2:9]1)=[O:6])[CH3:4].C1(C)C=CC=CC=1.[OH-].[Na+]>O>[CH3:1][CH2:2][C@@H:3]([C:5]([O:7][C@@H:8]1[C@@H:13]2[C@@H:14]([CH2:19][CH2:20][C@H:21]3[O:26][C:25](=[O:27])[CH2:24][C@H:23]([OH:28])[CH2:22]3)[C@@H:15]([CH3:18])[CH:16]=[CH:17][C:12]2=[CH:11][C@H:10]([CH3:30])[CH2:9]1)=[O:6])[CH3:4]

Participants

5

Reactant 3

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 64727Lovastatin Acid

Product 1

HCID 53232Lovastatin

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

The lovastatin acid in the extract was converted into the lactone by heating it to 90° C. for 3 hours (yield of conversion was 99.2%). After cooling to room temperature, the toluene was mixed with 80 ml of water, while the pH was adjusted to pH=10 with NaOH. After separation of the layers, the toluene layer was mixed again with 80 ml of fresh water, while the pH was adjusted to pH=4 with sulfuric acid. After separation of the layers, the toluene layer was treated with 0.1 g of active coal, Norit SX ultra. Subsequently the toluene solution was filtrated and further concentrated to 15 ml by evaporation. Cooling to -10° C. resulted in crystallization. The crystals were washed with 5 ml of cold toluene, and dried under vacuum at room temperature. In these crystals no 4-acetyl lovastatin could be detected, neither by TLC nor by proton NMR.

Workup

  1. temperatureAfter cooling to room temperature
  2. customAfter separation of the layers
  3. additionthe toluene layer was mixed again with 80 ml of fresh water, while the pH
  4. customAfter separation of the layers
  5. additionthe toluene layer was treated with 0.1 g of active coal, Norit SX ultra
  6. filtrationSubsequently the toluene solution was filtrated
  7. concentrationfurther concentrated to 15 ml by evaporation
  8. temperatureCooling to -10° C.
  9. customresulted in crystallization
  10. washThe crystals were washed with 5 ml of cold toluene
  11. customdried under vacuum at room temperature

Sources & evidence

ORD record
ord-abda88a6abdd43ffbfba02bc17799f14
Source dataset
uspto-grants-1999_11
Patent number
US05989877

Reaction notes

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