Dicyclohexylcarbodiimide → PravastatinLactone-d3

HRID 728513Notes

Reaction equation

HRID 728513 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]([OH:30])[CH2:9]1)=[O:6])[CH3:4].C1(N=C=NC2CCCCC2)CCCCC1.ON1C(=O)CCC1=O>CN(C)C=O>[CH3:4][CH:3]([CH2:2][CH3:1])[C:5]([O:7][CH:8]1[CH:13]2[C:12]([CH:17]=[CH:16][CH:15]([CH3:18])[CH:14]2[CH2:19][CH2:20][CH:21]2[CH2:22][CH:23]([OH:28])[CH2:24][C:25](=[O:26])[O:27]2)=[CH:11][CH:10]([OH:30])[CH2:9]1)=[O:6]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 54687PravastatinHCID 80170N-Hydroxysuccinimide

Product 1

HCID 9931183PravastatinLactone-d3Yield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a dry 100 ml round-bottomed flask equipped with a stir bar and CaSO4 drying tube was added 3.32 g (7.44 mmol) of pravastatin, 3.47 g (16.8 mmol) of dicyclohexylcarbodiimide (DCC), 1.93 g (16.8 mmol) of N-hydroxysuccinimide and 50 ml of dry dimethylformamide (DMF) (distilled from CaO) and the mixture stirred at room temperature for 16 hours. The resulting suspension was filtered and the filtrate evaporated at 30° C under reduced pressure. The residue was taken up in 50 ml of 20:1 CHCl3 :MeOH, filtered and evaporated. The resulting yellow oil was applied to 300 g of silica gel and eluted in a stepwise manner (1 liter of 40:1 CHCl3 :MeOH; 1 liter of 30:1 CHCl3 :MeOH, 1 liter of 20:1 CHCl3 :MeOH). The product was eluted with the 20:1 eluant. The good fractions (TLC, 8:1 CHCl3 isopropyl alcohol (IPA) were combined and evaporated and the resulting oil triturated with ether to yield 2.15 g (71%) of the title compound as a white powder.

Workup

  1. customTo a dry 100 ml round-bottomed flask equipped with a stir bar and CaSO4 drying tube
  2. filtrationThe resulting suspension was filtered
  3. customthe filtrate evaporated at 30° C under reduced pressure
  4. filtrationMeOH, filtered
  5. customevaporated
  6. washeluted in a stepwise manner (1 liter of 40:1 CHCl3 :MeOH; 1 liter of 30:1 CHCl3 :MeOH, 1 liter of 20:1 CHCl3 :MeOH)
  7. washThe product was eluted with the 20:1 eluant
  8. customevaporated
  9. customthe resulting oil triturated with ether

Sources & evidence

ORD record
ord-550efbf4fd4546a7b35d0f3da5642fed
Source dataset
uspto-grants-1991_09
Patent number
US05047549

Reaction notes

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