Water → Atorvastatin

HRID 883671Notes

Reaction equation

HRID 883671 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=[O:16])[C:7]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:34])[CH3:3].[OH-].[NH4+:43].O>C(#N)C>[CH3:3][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=[O:16])[C:7]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[C:6]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:34])[CH3:1].[NH4+:43].[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:7]2[N:8]([CH2:9][CH2:10][CH:11]([OH:19])[CH2:12][CH:13]([OH:18])[CH2:14][C:15]([O-:17])=[O:16])[C:4]([CH:2]([CH3:3])[CH3:1])=[C:5]([C:33]([NH:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:34])[C:6]=2[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 962WaterHCID 14923Ammonium HydroxideHCID 60823Atorvastatin2×

Product 2

HCID 60823AtorvastatinHCID 730592022-(4-Fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, ammonium salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

The ammonium salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (ACN) (0.634 g in 25 mL of ACN). A solution was prepared by dissolving 12.04 mg of ammonium hydroxide (1.0 equivalents) in acetonitrile (0.5 mL). The stock solution of atorvastatin free acid (2.24 mL) was added to the counterion solution with stirring. If a gel formed, additional acetonitrile and water was added as necessary. After 2 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with acetonitrile and air dried at ambient conditions to afford atorvastatin ammonium.

Workup

  1. customA solution was prepared
  2. customIf a gel formed
  3. stirringAfter 2 days of stirring at ambient temperature
  4. customthe solids were isolated by vacuum filtration
  5. filtrationfilter
  6. washThe solids were rinsed with acetonitrile and air
  7. customdried at ambient conditions

Sources & evidence

ORD record
ord-99e137fbcdfe463e805cdb2824fcfcdc
Source dataset
uspto-grants-2012_08
Patent number
US08236966B2

Reaction notes

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