Potassium Carbonate → 4-(2-Butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine

HRID 2069892Notes

Reaction equation

HRID 2069892 reaction equation
F[C:2]1[C:7]([F:8])=[C:6](F)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:16]([OH:20])[C:17]#[C:18][CH3:19].[CH3:21][CH:22]1[CH2:27][CH:26]([CH3:28])[CH2:25][NH:24][CH2:23]1>O.C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:16]([O:20][C:2]1[C:7]([F:8])=[C:6]([N:24]2[CH2:25][CH:26]([CH3:28])[CH2:27][CH:22]([CH3:21])[CH2:23]2)[N:5]=[CH:4][N:3]=1)[C:17]#[C:18][CH3:19]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 129912-Butyn-1-olHCID 1182593,5-DimethylpiperidineHCID 35727644,5,6-Trifluoropyrimidine

Product 1

HCID 593411354-(2-Butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidineYield 94%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
30 °C

Procedure

To a mixture obtained by adding 110.0 g of 4,5,6-trifluoropyrimidine, 114.6 g of potassium carbonate and 16.6 g of triethylamine to 220.0 g of toluene, 60.4 g of 2-butyn-1-ol was added dropwise at 25 to 30° C. over one hour, followed by stirring at 30° C. for 8 hours. Then, 220.0 g of water was added dropwise in the reaction mixture, followed by stirring for 14 hours. Then, 97.5 g of 3,5-dimethylpiperidine (a mixture of a cis-isomer and a trans-isomer in a mixing ratio of about 7:3) was added dropwise and, after the mixture was stirred at 30° C. for 6 hours, the reaction mixture was allowed to stand. After separating into the organic layer and the aqueous layer, the aqueous layer was removed and the organic layer was then washed once with 220.0 g of 5% hydrochloric acid and then washed once with 220.0 g of water. The organic layer was concentrated to obtain 213.8 g (yield: 94%) of 4-(2-butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine (hereinafter referred to as the present compound (3)). Product purity 96% (HPLC)

Workup

  1. customTo a mixture obtained
  2. additionwas added dropwise at 25 to 30° C. over one hour
  3. stirringby stirring for 14 hours
  4. additiona trans-isomer in a mixing ratio of about 7:3) was added dropwise
  5. stirringafter the mixture was stirred at 30° C. for 6 hours
  6. customAfter separating into the organic layer
  7. customthe aqueous layer, the aqueous layer was removed
  8. washthe organic layer was then washed once with 220.0 g of 5% hydrochloric acid
  9. washwashed once with 220.0 g of water
  10. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-67d9822c6fac4bc2ad0c20f2da389ed2
Source dataset
uspto-grants-2012_10
Patent number
US08299245B2

Reaction notes

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