Methanol → Atorvastatin calcium

HRID 1925664Notes

Reaction equation

HRID 1925664 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]([O-: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])[CH3:3].[Na+].CO.C([O-])(=O)C.[Ca+2:49].C([O-])(=O)C>O>[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]([O-: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].[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]([O-: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].[Ca+2:49]

Participants

5

Reactant 3

HCID 887MethanolHCID 6116Calcium AcetateHCID 23665101Sodium (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate

Product 1

HCID 60822Atorvastatin calcium

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

In a reactor, 213 g of the atorvastatin sodium salt, obtained in Example 6, was mixed with 1.0 L of methanol and 6.0 L of purified water, and the solution was then heated to 50° C. Then, the heated solution was slowly added dropwise to a solution of 0.5 molar equivalents of calcium acetate in 0.6 L of water in another reactor. After the completion of the addition, the mixture was slowly cooled to 15° C. with stirring for 2 hours, and then was filtered. The resulting solid was washed with 2 L of purified water, and then dried in a vacuum at 50° C., thus obtaining 205 g of atorvastatin hemicalcium salt.

Workup

  1. additionAfter the completion of the addition
  2. temperaturethe mixture was slowly cooled to 15° C.
  3. filtrationwas filtered
  4. washThe resulting solid was washed with 2 L of purified water
  5. customdried in a vacuum at 50° C.

Sources & evidence

ORD record
ord-bf00600095364ce2ae0b8f6a087da6db
Source dataset
uspto-grants-2012_05
Patent number
US08178697B2

Reaction notes

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