Potassium Carbonate → 4-(2-Butynyloxy)-6-(3-trifluoromethylpiperidino)pyrimidine

HRID 2069891Notes

Reaction equation

HRID 2069891 reaction equation
F[C:2]1[CH:7]=[C:6](F)[N:5]=[CH:4][N:3]=1.[C:9](=O)([O-])[O-].[K+].[K+].[CH2:15]([OH:19])[C:16]#[C:17][CH3:18].[F:20][C:21]([F:28])([F:27])[CH:22]1[CH2:26][CH2:25][NH:24][CH2:23]1>O.C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:15]([O:19][C:2]1[CH:7]=[C:6]([N:24]2[CH2:25][CH2:9][CH2:26][CH:22]([C:21]([F:20])([F:27])[F:28])[CH2:23]2)[N:5]=[CH:4][N:3]=1)[C:16]#[C:17][CH3:18]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 129912-Butyn-1-olHCID 1377174,6-DifluoropyrimidineHCID 51521593-(Trifluoromethyl)pyrrolidine

Product 1

HCID 576729514-(2-Butynyloxy)-6-(3-trifluoromethylpiperidino)pyrimidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
30 °C

Procedure

To a mixture obtained by adding 110.0 g of 4,6-difluoropyrimidine, 132.3 g of potassium carbonate and 19.2 g of triethylamine to 220.0 g of toluene, 69.8 g of 2-butyn-1-ol is added dropwise at 25 to 30° C. over one hour, followed by stirring at 30° C. Then, 220.0 g of water is added dropwise into the reaction mixture, followed by stirring. Then, 152.4 g of 3-trifluoromethylpyrrolidine is added dropwise and, after the mixture is stirred at 30° C., the reaction mixture is allowed to stand. After separating into the organic layer and the aqueous layer, the aqueous layer is removed and the organic layer is washed once with 220.0 g of 5% hydrochloric acid and then washed once with 220.0 g of water. The organic layer is concentrated to obtain 4-(2-butynyloxy)-6-(3-trifluoromethylpiperidino)pyrimidine (hereinafter referred to as the present compound (2)).

Workup

  1. customTo a mixture obtained
  2. additionis added dropwise at 25 to 30° C. over one hour
  3. stirringby stirring
  4. stirringafter the mixture is stirred at 30° C.
  5. customAfter separating into the organic layer
  6. customthe aqueous layer, the aqueous layer is removed
  7. washthe organic layer is washed once with 220.0 g of 5% hydrochloric acid
  8. washwashed once with 220.0 g of water
  9. concentrationThe organic layer is concentrated

Sources & evidence

ORD record
ord-7e674331cfe14eaaafee9cbb79f9b92b
Source dataset
uspto-grants-2012_10
Patent number
US08299245B2

Reaction notes

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