Hydrochloric Acid → Pitavastatin

HRID 445950

Reaction equation

HRID 445950 reaction equation
C(NC(C)C)(C)C.[CH:8]1([C:11]2[C:20](/[CH:21]=[CH:22]/[C@@H:23]([OH:31])[CH2:24][C@@H:25]([OH:30])[CH2:26][C:27]([OH:29])=[O:28])=[C:19]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH2:10][CH2:9]1.Cl.[OH-].[Na+].O.O.[Cl-].[Ca+2].[Cl-]>O.C(OCC)(=O)C>[CH:8]1([C:11]2[C:20](/[CH:21]=[CH:22]/[C@@H:23]([OH:31])[CH2:24][C@@H:25]([OH:30])[CH2:26][C:27]([OH:29])=[O:28])=[C:19]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 6093260Calcium chloride, dihydrateHCID 60150999HCID 60150999, compound

Product 1

HCID 5282452PitavastatinYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid diisopropylamine salt (10.0 g) in a mixed solvent of ethyl acetate (100.0 mL) and water (100.0 mL) was cooled to 0˜5° C. The pH of the reaction mixture was adjusted to 3.0˜4.0 using 1N hydrochloric acid solution. Water (40.0 mL) was added to the separated organic layer, the pH of which was then adjusted to 9.0˜11.5 using 1N sodium hydroxide solution. Calcium chloride dihydrate (2.8 g) was added to the separated water layer. The reaction mixture was stirred at 20˜25° C. for 2 hours and then filtered under reduced pressure. The resulting white solid was dried to obtain (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid 1/2 calcium salt (6.9 g, yield 90%).

Workup

  1. filtrationfiltered under reduced pressure
  2. customThe resulting white solid was dried

Sources & evidence

ORD record
ord-b4cfd5bab0f64a8cbc35a95f638e6bdc
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Linked notes

Loading…