Isopropanol → sodium;(E)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate

HRID 2219842Notes

Reaction equation

HRID 2219842 reaction equation
[CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33].CC(O)C>O>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]

Participants

5

Reactant 3

HCID 3776Isopropanol3×HCID 14798Sodium HydroxideHCID 13741557Fluvastatin methyl ester

Product 1

HCID 16760425sodium;(E)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoateYield 22.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Fluvastatin methyl ester (2.0 g) was added to a solution of NaOH (1 eq.) in water. The mixture was stirred at about 70° C. for 2 h until the raw material wasn't observed by HPLC. After this time, propan-2-ol (10 ml) was dripped and the solution was cooled slowly to room temperature. Another 40 ml of propan-2-ol (in 3 portions) were added at room temperature to the solution but no precipitation was ° C. curred. The solution was stirred overnight and a gel-like precipitate formed. The mixture was heated to reflux to dissolve the gel. The mixture was then allowed to cool to room temperature. A yellow slurry was obtained. After stirring overnight, another 15 ml of propan-2-ol were added dropwise. The product was isolated by filtration under nitrogen, washed with propan-2-ol (25 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 0.46 g (22.6%) of fluvastatin sodium Form XLIII.

Workup

  1. customno precipitation
  2. customa gel-like precipitate formed
  3. temperatureThe mixture was heated
  4. temperatureto reflux
  5. dissolutionto dissolve the gel
  6. temperatureto cool to room temperature
  7. customA yellow slurry was obtained
  8. stirringAfter stirring overnight
  9. customThe product was isolated by filtration under nitrogen
  10. washwashed with propan-2-ol (25 ml)
  11. customdried at 50° C. in a vacuum oven for 24 h

Sources & evidence

ORD record
ord-828c1fa79ac44656897dc4e52f1e4866
Source dataset
uspto-grants-2008_08
Patent number
US07414140B2

Reaction notes

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