Water → 4-[5-(5,5-Dimethyl-[1,3]dioxan-2-yl)-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-pyridine

HRID 1454290Notes

Reaction equation

HRID 1454290 reaction equation
[CH3:1][O:2][CH:3]([O:22][CH3:23])[C:4]1[CH:5]=[C:6]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[N:7]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[N:8]=1.[CH3:24][C:25](C)(CO)[CH2:26]O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH3:24][C:25]1([CH3:26])[CH2:23][O:22][CH:3]([C:4]2[CH:5]=[C:6]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[N:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[N:8]=2)[O:2][CH2:1]1

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 31344Neopentyl glycolHCID 536347204-[5-dimethoxymethyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-pyridine

Product 1

HCID 99065424-[5-(5,5-Dimethyl-[1,3]dioxan-2-yl)-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-pyridineYield 29.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 4-[5-dimethoxymethyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-pyridine (3 g, Reference Example 1), 2,2-dimethylpropane-1,3-diol (2.2 g) and p-toluene sulfonic acid (2 g) in dry toluene (50 ml) was refluxed for 1 hour with azeotropic removal of water. The reaction mixture was cooled to room temperature then evaporated. The residue was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium carbonate solution (50 ml). The organic phase was washed three times with water (50 ml), then dried over magnesium sulphate and then evaporated. The residual oil was triturated twice with diethyl ether then recrystallised from diethyl ether to give the title compound as white needles (1 g), m.p. 150-151° C. [Elemental analysis: C,67.69; H,5.98; N,12.09%. Calculated for C20H20FN3O2: C,67.97; H,5.70; N,11.89%]. MS: 354 [MH]+. RF=0.42 (ethyl acetate, determined by thin layer chromatography on silica).

Workup

  1. customthen evaporated
  2. customThe residue was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium carbonate solution (50 ml)
  3. washThe organic phase was washed three times with water (50 ml)
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe residual oil was triturated twice with diethyl ether
  7. customthen recrystallised from diethyl ether

Sources & evidence

ORD record
ord-8c9e132cdd3d49a4aee1cd0b3506878a
Source dataset
uspto-grants-2009_01
Patent number
US07479501B2

Reaction notes

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