Hydrochloric Acid → Rosuvastatin

HRID 222523

Reaction equation

HRID 222523 reaction equation
[CH3:1][CH:2]([C:4]1[C:9](/[CH:10]=[CH:11]/[C@@H:12]([OH:24])[CH2:13][C@@H:14]([OH:23])[CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])=[C:8]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[N:7]=[C:6]([N:32]([S:34]([CH3:37])(=[O:36])=[O:35])[CH3:33])[N:5]=1)[CH3:3].[OH-].[Na+].[Na].Cl>C1COCC1.O>[CH3:3][CH:2]([C:4]1[N:5]=[C:6]([N:32]([S:34]([CH3:37])(=[O:35])=[O:36])[CH3:33])[N:7]=[C:8]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:9]=1/[CH:10]=[CH:11]/[C@@H:12]([OH:24])[CH2:13][C@@H:14]([OH:23])[CH2:15][C:16]([OH:18])=[O:17])[CH3:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5360545SodiumHCID 114782101,1-Dimethylethyl (3R,5S,6E)-7-(4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoate

Product 1

HCID 446157RosuvastatinYield 105.4%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
30 °C

Procedure

Rosuvastatin tert-butyl ester (27.0 g, 50.2 mmol) is dissolved in 225 mL of a 4:1 mixture of THF/water. The clear solution is warmed to 30° C. and 8.0 M NaOH (6.75 mL, 54.0 mmol) is added portionwise. The reaction mixture is stirred at 30° C. for 2 hours giving a clear yellow solution. Then THF is removed completely under the reduced pressure (20 mbar) at 40° C. The remaining aqueous solution is diluted with water to 225 mL and washed with AcOEt (3×90 mL). To a vigorously stirring solution of sodium rosuvastatinate is added dropwise HCl 37% (4.2 mL, 50.2 mmol) at ambient temperature. The obtained white emulsion of a free acid is extracted with AcOEt (150 mL). After separation from the organic layer aqueous phase is additionaly extracted with AcOEt (2×50 mL). Organic layers are combined and washed with water (3×30 mL). Then AcOEt is removed under reduced pressure (20 mbar) at 40° C. The residue is dissolved in a minimal amount of acetonitrile (MeCN) and the solvent is rapidly evaporated under reduced pressure (20 mbar) at 40° C. to give 25.48 g of the solid residue of free rosuvastatin acid.

Workup

  1. customgiving a clear yellow solution
  2. customThen THF is removed completely under the reduced pressure (20 mbar) at 40° C
  3. additionThe remaining aqueous solution is diluted with water to 225 mL
  4. washwashed with AcOEt (3×90 mL)
  5. extractionThe obtained white emulsion of a free acid is extracted with AcOEt (150 mL)
  6. customAfter separation from the organic layer aqueous phase
  7. extractionis additionaly extracted with AcOEt (2×50 mL)
  8. washwashed with water (3×30 mL)
  9. customThen AcOEt is removed under reduced pressure (20 mbar) at 40° C
  10. dissolutionThe residue is dissolved in a minimal amount of acetonitrile (MeCN)
  11. customthe solvent is rapidly evaporated under reduced pressure (20 mbar) at 40° C.

Sources & evidence

ORD record
ord-99a3cd9478594e74aa1e4764a00ab599
Source dataset
uspto-grants-2012_06
Patent number
US08207333B2

Linked notes

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