Cesium carbonate → 2-Chloro-5-[(2,2,5-trimethyl-1,3-dioxan-5-yl)methoxy]pyrimidine

HRID 632607Notes

Reaction equation

HRID 632607 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:20][C:21]1([CH3:29])[CH2:26][O:25][C:24]([CH3:28])([CH3:27])[O:23][CH2:22]1)(=O)=O>CN(C)C=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:20][C:21]2([CH3:29])[CH2:26][O:25][C:24]([CH3:28])([CH3:27])[O:23][CH2:22]2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 145957002-Chloro-5-pyrimidinolHCID 866824725-(Methanesulfonyloxymethyl)-2,2,5-trimethyl-1,3-dioxane

Product 1

HCID 866824712-Chloro-5-[(2,2,5-trimethyl-1,3-dioxan-5-yl)methoxy]pyrimidineYield 30.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 9.50 g (72.8 mmol) of 2-chloro-5-hydroxypyrimidine in 100 ml of N,N-dimethylformamide, 26.1 g (80.1 mmol) of cesium carbonate and 24.3 g (102 mmol) of 5-(methanesulfonyloxymethyl)-2,2,5-trimethyl-1,3-dioxane, which was synthesized by the method described in V. W. Gash, Journal of Organic Chemistry, 1972, Vol. 37, p. 2197-2201, were added, and the mixture was stirred at 90° C. for 24 hours. After completion of the reaction, the insoluble material was filtered off and washed with ethyl acetate, and then 0.5 N sodium hydroxide aqueous solution was added to the filtrate and separation was performed. The obtained aqueous layer was further extracted with ethyl acetate. The obtained organic layers were combined, washed with water and saturated sodium chloride aqueous solution in order and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. Toluene was added to the obtained residue, and the precipitate was obtained by filtration and washed with toluene and n-heptane to provide 6.00 g of the title compound as a white solid (yield: 30%).

Workup

  1. addition2197-2201, were added
  2. customAfter completion of the reaction
  3. filtrationthe insoluble material was filtered off
  4. washwashed with ethyl acetate
  5. addition0.5 N sodium hydroxide aqueous solution was added to the filtrate and separation
  6. extractionThe obtained aqueous layer was further extracted with ethyl acetate
  7. washwashed with water and saturated sodium chloride aqueous solution in order
  8. dry with materialdried with anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. additionToluene was added to the obtained residue
  11. customthe precipitate was obtained by filtration
  12. washwashed with toluene and n-heptane

Sources & evidence

ORD record
ord-1e032c165a5848fb9fe8ef59d75a86f6
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

Loading…