Methane → Simvastatin

HRID 1271614Notes

Reaction equation

HRID 1271614 reaction equation
C[CH2:2][C:3]([C:6]([O:8][C@@H:9]1[C@@H:14]2[C@@H:15]([CH2:20][CH2:21][C@@H:22](O)[CH2:23][C@@H:24]([OH:29])[CH2:25][C:26]([O-:28])=[O:27])[C@@H:16]([CH3:19])[CH:17]=[CH:18][C:13]2=[CH:12][C@H:11]([CH3:31])[CH2:10]1)=[O:7])([CH3:5])[CH3:4].[NH4+].[CH4:33]>C1(C)C=CC=CC=1>[CH3:33][CH2:4][C:3]([C:6]([O:8][C@@H:9]1[C@@H:14]2[C@@H:15]([CH2:20][CH2:21][C@H:22]3[O:27][C:26](=[O:28])[CH2:25][C@H:24]([OH:29])[CH2:23]3)[C@@H:16]([CH3:19])[CH:17]=[CH:18][C:13]2=[CH:12][C@H:11]([CH3:31])[CH2:10]1)=[O:7])([CH3:5])[CH3:2]

Participants

4

Reactant 2

HCID 297MethaneHCID 10961424Simvastatin ammonium salt

Product 1

HCID 54454Simvastatin

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The ammonium salt of step 3 (15 gm) is suspended in toluene (500 ml) and heated at 100° C. under a constant sweep of nitrogen for 5 hours. The solution is cooled to 25° C., activated charcoal (1 gm) is added stirred for 30 minutes and then filtered through celite-bed. The filtrate is concentrated under reduced pressure to a volume of 70 ml. Cyclohexane (200 ml) is added, refluxed for 20 minutes, cooled to 10° C. and stirred for 3 hours at 10° C. The precipitated solid is filtered and washed with cold cyclohexane (100 ml) and dried to obtain simvastatin as white crystalline product. The product is re-crystallized from absolute ethanol to obtain 13 gm of simvastatin (HPLC Purity 99.7%).

Workup

  1. temperatureThe solution is cooled to 25° C.
  2. filtrationfiltered through celite-bed
  3. concentrationThe filtrate is concentrated under reduced pressure to a volume of 70 ml
  4. additionCyclohexane (200 ml) is added
  5. temperaturerefluxed for 20 minutes
  6. temperaturecooled to 10° C.
  7. stirringstirred for 3 hours at 10° C
  8. filtrationThe precipitated solid is filtered
  9. washwashed with cold cyclohexane (100 ml)
  10. customdried

Sources & evidence

ORD record
ord-65c6c400633e4abaa938afec8e6859ae
Source dataset
uspto-grants-2007_04
Patent number
US07205415B2

Reaction notes

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