Water → Atorvastatin calcium propylene glycol solvate

HRID 1173814Notes

Reaction equation

HRID 1173814 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: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].[CH3:42][CH:43]([C:45]1[N:49]([CH2:50][CH2:51][C@@H:52]([OH:60])[CH2:53][C@@H:54]([OH:59])[CH2:55][C:56]([O-:58])=[O:57])[C:48]([C:61]2[CH:62]=[CH:63][C:64]([F:67])=[CH:65][CH:66]=2)=[C:47]([C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=2)[C:46]=1[C:74]([NH:76][C:77]1[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=1)=[O:75])[CH3:44].[Ca+2:83].C([O:87][CH:88]([CH3:90])[CH3:89])(=O)C.[OH2:91]>C(O)C(O)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]([O-: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])[CH3:1].[CH3:44][CH:43]([C:45]1[N:49]([CH2:50][CH2:51][C@@H:52]([OH:60])[CH2:53][C@@H:54]([OH:59])[CH2:55][C:56]([O-:58])=[O:57])[C:48]([C:61]2[CH:62]=[CH:63][C:64]([F:67])=[CH:65][CH:66]=2)=[C:47]([C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=2)[C:46]=1[C:74]([NH:76][C:77]1[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=1)=[O:75])[CH3:42].[CH3:89][CH:88]([OH:87])[CH2:90][OH:91].[Ca+2:83]

Participants

5

Reactant 3

HCID 962WaterHCID 7915Isopropyl AcetateHCID 60822Atorvastatin calcium

Product 1

HCID 51039411Atorvastatin calcium propylene glycol solvate

Reagents, catalysts & solvents 1

HCID 1030Propylene GlycolSolvent

Conditions

Temperature
57.5 °C

Procedure

Atorvastatin calcium (130 g) was dissolved in racemic propylene glycol followed by the addition of 7 parts of isopropyl acetate and 0.6 parts of water. The resulting mixture was warmed to 55-60° C. and stirred for 8-10 hours to afford a white suspension. The suspension was cooled to 20-25° C. and filtered and the filter-cake was rinsed with 2 parts of isopropyl acetate to provide 110 g of atorvastatin calcium propylene glycol solvate after drying in a vacuum oven at 50-60° C. Propylene glycol content: 6% by NMR, KF=0.2%. The DSC and IR of this material are shown as FIGS. 7 and 8 respectively.

Workup

  1. customto afford a white suspension
  2. temperatureThe suspension was cooled to 20-25° C.
  3. filtrationfiltered
  4. washthe filter-cake was rinsed with 2 parts of isopropyl acetate

Sources & evidence

ORD record
ord-4c56213224644dfe8a2b95b526133812
Source dataset
uspto-grants-2010_11
Patent number
US07834195B2

Reaction notes

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