Toluene → 4-Fluorophenyl-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidine

HRID 1915020Notes

Reaction equation

HRID 1915020 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.C1(C)C=CC=CC=1.[F:36][C:37]([F:43])([F:42])[S:38](Cl)(=[O:40])=[O:39]>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:37]([F:43])([F:42])[F:36])(=[O:40])=[O:39])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 79000Trifluoromethanesulfonyl chlorideHCID 178496923Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate

Product 1

HCID 179896104-Fluorophenyl-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidineYield 66.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

In a 300 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 2.9 g (10.0 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine, 1.7 g (16.8 mmol.) of triethylamine, and 50 mL of toluene. The mixture in the flask was chilled to 0° C. in an ice bath. To the chilled mixture was slowly added 2.4 g (14.1 mmol.) of trifluoromethanesulfonyl chloride, and the resulting mixture was subjected to reaction for 3 hours at the same temperature. After the reaction was complete, to the reaction mixture was added 30 mL of water. From the aqueous reaction mixture, an organic liquid portion was separated. The organic liquid portion was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (8:2, volume ratio)). There was obtained 2.8 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidine having the below-mentioned characteristics as a colorless oil. The yield was 66% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

Workup

  1. customIn a 300 mL-volume glass flask equipped with a stirrer
  2. customthe resulting mixture was subjected to reaction for 3 hours at the same temperature
  3. customFrom the aqueous reaction mixture, an organic liquid portion was separated
  4. concentrationThe organic liquid portion was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (8:2, volume ratio))

Sources & evidence

ORD record
ord-d440262a4386406a875e271e5118cb72
Source dataset
uspto-grants-2013_12
Patent number
US08614320B2

Reaction notes

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