Atorvastatin calcium → HCID 70680954, compound

HRID 350762Notes

Reaction equation

HRID 350762 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]>C(OCC)(=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]([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].[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]([OH:58])=[O:57])[C:48]([C:61]2[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=2)=[C:47]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[C:46]=1[C:74]([NH:76][C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)=[O:75])[CH3:42]

Participants

3

Reactant 1

HCID 60822Atorvastatin calcium

Product 1

HCID 70680954HCID 70680954, compoundYield 59.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5.0 g (8.6 mmole) of atorvastatin calcium was dissolved in 300 mL ethyl acetate and washed with 300 mL 10% (w/v) aqueous sodium hydrogen sulfate solution (pH 3). The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure to afford 2.85 g (5.11 mmole) of atorvastatin acid. This material was dissolved in 300 mL anhydrous toluene and heated at 60° C. for 40 hours, at which time analytical thin-layer chromatography using 4:1 methylene chloride:acetone eluent indicated near-complete conversion of the starting acid to a less polar product. The toluene was removed under reduced pressure and the reaction mixture was fractionated on 300 cc of silica gel using 4:1 methylene chloride: acetone eluent to afford, after combining, concentrating and drying of the appropriate fractions, 2.14 g (3.96 mmol, 46% overall) of atorvastatin lactone as a white foam. The 400 MHz 1H nuclear magnetic resonance (NMR) spectrum and the electrospray mass spectrum (ES-MS) were consistent with the lactone product. 1H NMR (Me2SO-d6) δ 9.80 (s, 1H), 7.49 (d, 2H), 7.25–7.15 (m, 6H), 7.05 (s, 4H), 6.99 (t, 2H), 5.15 (d, 1H), 4.46 (br s, 1H), 4.02 (s, 1H), 3.97 (m, 1H), 3.89 (m, 1H), 3.21 (q, 1H), 2.55 (dd, 1H), 2.32 (dd, 1H), 1.74 (br s, 2H), 1.6 (m, 2H), 1.36 (d, 6H). ES-MS: obsvd. m/z 541 ([MH]+).

Workup

  1. washwashed with 300 mL 10% (w/v) aqueous sodium hydrogen sulfate solution (pH 3)
  2. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-b1e64d4e22854f89bb53c43cef445f13
Source dataset
uspto-grants-2007_02
Patent number
US07183285B2

Reaction notes

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