Acetonitrile → Rosuvastatin Impurity 162

HRID 1515140Notes

Reaction equation

HRID 1515140 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([OH:21])[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.C(#N)C.[C:32]1([CH3:42])[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]([CH3:19])[CH3:20])[N:11]=[C:10]([O:21][S:38]([C:35]3[CH:36]=[CH:37][C:32]([CH3:42])=[CH:33][CH:34]=3)(=[O:40])=[O:39])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 178496923Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate

Product 1

HCID 17989602Rosuvastatin Impurity 162Yield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

In a 200 mL-volume glass flask were placed 27.6 g (95.1 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine, 12.5 g (123 mmol.) of triethylamine, and 95 mL of acetonitrile. The mixture of the flask was chilled to 0-5° C. in an ice bath. To the chilled mixture was slowly added 20.0 g (105 mmol.) of p-toluenesulfonyl chloride, and the resulting mixture was subjected to reaction at 20-25° C. for one hour. After the reaction was complete, to the reaction mixture was added 95 mL of water. The aqueous reaction mixture was extracted with toluene and the toluene portion was separated. The toluene portion was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The dried mixture was filtered and concentrated under reduced pressure. The residue was crystallized from methanol, to give 35.9 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)-pyrimidine as a colorless crystalline product having the below-mentioned characteristics. The yield was 85% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

Workup

  1. additionThe mixture of the flask
  2. customthe resulting mixture was subjected to reaction at 20-25° C. for one hour
  3. extractionThe aqueous reaction mixture was extracted with toluene
  4. customthe toluene portion was separated
  5. washThe toluene portion was washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe dried mixture was filtered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was crystallized from methanol

Sources & evidence

ORD record
ord-46db1f84f1c042eb875d4053f7b69a36
Source dataset
uspto-grants-2012_07
Patent number
US08222412B2

Reaction notes

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