Tert-Butylamine → Rosuvastatin

HRID 578740

Reaction equation

HRID 578740 reaction equation
[CH3:1][CH:2]([C:4]1[N:9]=[C:8]([N:10]([S:12]([CH3:15])(=[O:14])=[O:13])[CH3:11])[N:7]=[C:6]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[C:5]=1/[CH:23]=[CH:24]/[C@@H:25]([OH:33])[CH2:26][C@@H:27]([OH:32])[CH2:28][C:29]([OH:31])=[O:30])[CH3:3].C([NH-])CCC.O.C(O)C.C(N)(C)(C)C>CC(O)C>[CH3:3][CH:2]([C:4]1[N:9]=[C:8]([N:10]([S:12]([CH3:15])(=[O:13])=[O:14])[CH3:11])[N:7]=[C:6]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[C:5]=1/[CH:23]=[CH:24]/[C@@H:25]([OH:33])[CH2:26][C@@H:27]([OH:32])[CH2:28][C:29]([OH:31])=[O:30])[CH3:1]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 19096565Water ethanolHCID 86699893Rosuvastatin n-butylamide

Product 1

HCID 446157RosuvastatinYield 115.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

An autoclave having 800 cm3 volume is charged with 16.1 g (0.03 mol) of rosuvastatin n-butylamide, 644 cm3 of water/ethanol (9:1, v/v) solvent mixture and 43.9 g (63.3 cm3; 0.60 mol) tert-butylamine. The reaction mixture is stirred for 24 hours at 120° C. The mixture is allowed to cool to room temperature, diluted with 2-propanol and evaporated in vacuo. The evaporation residue is stirred in the mixture of tert-butylmethylether and heptane (2:5, v/v) and the crystals are filtered. Thus 16.7 g (100%) of rosuvastatin TBA salt are obtained. The crude salt is boiled in the mixture of acetonitrile and 2-propanol (8.6:1, v/v), stirred at room temperature, filtered, washed and dried. The product thus obtained is boiled in acetonitrile, 2-propanol are added to the boiling mixture, decolorized with carbon and filtered. The precipitated crystals are filtered and washed with acetonitrile. In this way 10.7 g (64%) of rosuvastatin TBA salt having a purity (as determined by HPLC) greater than 99.5% are obtained.

Workup

  1. temperatureto cool to room temperature
  2. customevaporated in vacuo
  3. stirringThe evaporation residue is stirred in the mixture of tert-butylmethylether and heptane (2:5
  4. filtrationv/v) and the crystals are filtered

Sources & evidence

ORD record
ord-0aab72b7e0b94ea7bffe4e15c0a3a5f1
Source dataset
uspto-grants-2015_05
Patent number
US09040696B2

Linked notes

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