Acetonitrile → 4-(4-Fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-methanesulfonyloxypyrimidine

HRID 1915017Notes

Reaction equation

HRID 1915017 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.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>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:33]([CH3:32])(=[O:35])=[O:34])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 178496923Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate

Product 1

HCID 179896124-(4-Fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-methanesulfonyloxypyrimidineYield 89.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

In a 100 mL-volume glass flask were placed 10.0 g (34.4 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine, 5.22 g (58.5 mmol.) of triethylamine, and 34 mL of acetonitrile. The mixture in the flask was chilled to 0-5° C. in an ice bath. To the chilled mixture was slowly added 5.12 g (44.7 mmol.) of methanesulfonyl chloride, and the resulting mixture was subjected to reaction at 20-25° C. for 2 hours. After the reaction was complete, to the reaction mixture was added 60 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 11.3 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-methanesulfonyloxypyrimidine as a colorless crystalline product having the below-mentioned characteristics. The yield was 89% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

Workup

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

Sources & evidence

ORD record
ord-1edbdda60688437fa4007a2d0f02a2f2
Source dataset
uspto-grants-2013_12
Patent number
US08614320B2

Reaction notes

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