Phosphorus oxychloride → Methyl 2-chloro-4-(4-fluorophenyl)-6-isopropylpyrimidine-5-carboxylate

HRID 968900

Reaction equation

HRID 968900 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](O)[N:9]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:24])=O.C(=O)([O-])O.[Na+]>>[Cl:24][C:10]1[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178496923Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate

Product 1

HCID 11220571Methyl 2-chloro-4-(4-fluorophenyl)-6-isopropylpyrimidine-5-carboxylateYield 97.3%

Conditions

Temperature
103 °C

Procedure

In a 25 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 1.00 g (3.43 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine and 3.4 mL (3.7 mmol.) of phosphorus oxychloride. The mixture was heated to 100-106° C. for 1.5 hours under refluxing, to carry out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature, and poured into an ice/water mixture. The resulting aqueous mixture was neutralized with a saturated aqueous sodium hydrogen carbonate solution. The neutralized aqueous mixture was extracted with ethyl acetate. The ethyl acetate portion was separated, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The dried ethyl acetate portion was filtered and concentrated under reduced pressure, to obtain 1.03 g of 2-chloro-4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonylpyrimidine as a colorless crystalline product having the below-mentioned characteristics. The yield was 97% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

Workup

  1. customIn a 25 mL-volume glass flask equipped with a stirrer
  2. temperatureunder refluxing
  3. customreaction
  4. temperaturethe reaction mixture was cooled to room temperature
  5. extractionThe neutralized aqueous mixture was extracted with ethyl acetate
  6. customThe ethyl acetate portion was separated
  7. washwashed with a saturated aqueous sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe dried ethyl acetate portion was filtered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-03e56e2d78cc4c30bd7b8bbbed45d799
Source dataset
uspto-grants-2007_12
Patent number
US07304156B2

Linked notes

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