Triethylamine → Homopravastatin Lactone Di-(tert-butyldimethylsilyl) Ether

HRID 400136Notes

Reaction equation

HRID 400136 reaction equation
C(N(CC)CC)C.P(Cl)(OCC)(OCC)=O.[CH3:17][C@@H:18]([CH2:22][CH2:23][CH3:24])[C:19]([OH:21])=[O:20].[Si:25]([O:32][C@H:33]1[CH2:42][C@H:41](O)[C@H:40]2[C:35]([CH:36]=[CH:37][C@H:38]([CH3:61])[C@@H:39]2[CH2:44][CH2:45][C@H:46]2[O:51][C:50](=[O:52])[CH2:49][C@H:48]([O:53][Si:54]([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55])[CH2:47]2)=[CH:34]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].N1(C2C=CN=CC=2)CCCC1>C1C=CC=CC=1>[Si:25]([O:32][C@H:33]1[CH2:42][C@H:41]([O:20][C:19](=[O:21])[C@@H:18]([CH3:17])[CH2:22][CH2:23][CH3:24])[C@H:40]2[C:35]([CH:36]=[CH:37][C@H:38]([CH3:61])[C@@H:39]2[CH2:44][CH2:45][C@H:46]2[O:51][C:50](=[O:52])[CH2:49][C@H:48]([O:53][Si:54]([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:55])[CH3:56])[CH2:47]2)=[CH:34]1)([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 13139Diethyl chlorophosphateHCID 755674-PyrrolidinopyridineHCID 642231(+)-2-Methylpentanoic acidHCID 14600906Pravastatin Diol Lactone Di-(tert-butyldimethylsilyl) Ether

Product 1

HCID 54016254Homopravastatin Lactone Di-(tert-butyldimethylsilyl) EtherYield 74%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

690 mg (6.8 mmol) of triethylamine and 713 mg (4.1 mmol) of diethyl chlorophosphate were added to a solution of 400 mg (3.4 mmol) of (S)-2-methylvaleric acid in 15 ml of dry benzene, and the resulting mixture was stirred at room temperature for one hour. 1.58 g (2.9 mmol) of (4R,6R)-6-{2-[(1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above] and 250 mg (1.7 mmol) of 4-(1-pyrrolidinyl)pyridine were then added to the mixture. The mixture was then stirred at room temperature for 24 hours, after which the mixture was diluted with 20 ml of benzene. The diluted mixture was then washed with 20 ml of water, 20 ml of a 10% w/v aqueous solution of citric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, in that order. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by flash column chromatography through silica gel, using a 6:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.38 g (74% yield) of the title compound.

Workup

  1. stirringThe mixture was then stirred at room temperature for 24 hours
  2. washThe diluted mixture was then washed with 20 ml of water, 20 ml of a 10% w/v aqueous solution of citric acid
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was removed by distillation under reduced pressure
  5. customThe resulting residue was purified by flash column chromatography through silica gel
  6. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-7099bccbf04342788bd911a0bdb8f226
Source dataset
uspto-grants-1998_10
Patent number
US05827855

Reaction notes

Loading…