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

HRID 968901

Reaction equation

HRID 968901 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.S(Cl)([Cl:24])=O.C1(C)C=CC=CC=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[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

6

Reactant 4

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 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 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °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, 0.5 mL (3.9 mmol.) of thionyl chloride, 3.44 mL of toluene, and 0.11 mL of N,N-dimethylformamide. The mixture was heated to 80° C. for 3 hours, 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 0.80 g of 2-chloro-4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonylpyrimidine as a colorless crystalline product. The yield was 76% (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. customreaction
  3. temperaturethe reaction mixture was cooled to room temperature
  4. extractionThe neutralized aqueous mixture was extracted with ethyl acetate
  5. customThe ethyl acetate portion was separated
  6. washwashed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe dried ethyl acetate portion was filtered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e0b29972e28c454ca266bd09ae471b1c
Source dataset
uspto-grants-2007_12
Patent number
US07304156B2

Linked notes

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