Water → Rosuvastatin

HRID 578741

Reaction equation

HRID 578741 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(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 962WaterHCID 6385Tert-ButylamineHCID 86699893Rosuvastatin n-butylamide

Product 1

HCID 446157RosuvastatinYield 112.1%

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) rosuvastatin n-butylamide, 644 cm3 of water and 43.9 g (63.3 cm3; 0.60 mol) tert-butylamine. The reaction mixture is stirred for 24 hours at the temperature of 120° C. The reaction mixture is allowed to cool to room temperature, diluted with 2-propanol and evaporated in vacuo. The residue is stirred in tert-butylmethylether-heptane mixture (2:5, v/v) and the crystals are filtered. Thus 16.2 g (99%) of crude 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 suspended in water and tert-butylamine (13 cm3) are added. The mixture is allowed to stand for four days and filtered. The mother lye is allowed to stand for further three days and the precipitated product is filtered, washed and dried. In this way, 4.33 g (25%) Form II rosuvastatin tert-butylammonium salt having the powder X-ray diffractogram of FIG. 1 are obtained.

Workup

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

Sources & evidence

ORD record
ord-b10466f342164fc5bed8cf55cc83cfc7
Source dataset
uspto-grants-2015_05
Patent number
US09040696B2

Linked notes

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