Potassium Carbonate → 2-Chloro-5-(ethoxymethoxy)pyrimidine

HRID 2066631Notes

Reaction equation

HRID 2066631 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.[CH2:9]([O:11][CH2:12]Cl)[CH3:10].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:12][O:11][CH2:9][CH3:10])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18523Chloromethyl ethyl etherHCID 145957002-Chloro-5-pyrimidinol

Product 1

HCID 866505392-Chloro-5-(ethoxymethoxy)pyrimidineYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred mixture of 2-chloro-5-pyrimidinol (107) (1.00 g, 7.66 mmol) and chloromethyl ethyl ether (1.75 mL, 18.9 mmol) in anhydrous DMF (2.5 mL) was treated with K2CO3 (2.15 g, 15.6 mmol). After stirring at room temperature for 16 h, the mixture was added to ice/aqueous NaHCO3 (100 mL) and extracted with 50% Et2O/petroleum ether (5×100 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% Et2O/petroleum ether firstly gave foreruns, and then further elution with 1-10% Et2O/petroleum ether gave 2-chloro-5-(ethoxymethoxy)pyrimidine (108) (1.27 g, 88%) as an oil; 1H NMR (CDCl3) δ 8.43 (s, 2H), 5.27 (s, 2H), 3.74 (q, J=7.1 Hz, 2H), 1.23 (t, J=7.1 Hz, 3 H); HRESIMS calcd for C7H10ClN2O2 m/z [M+H]+ 191.0396, 189.0425. found 191.0397, 189.0426.

Workup

  1. extractionextracted with 50% Et2O/petroleum ether (5×100 mL)
  2. customThe combined extracts were evaporated to dryness
  3. customthe residue was chromatographed on silica gel
  4. washElution with 0-1% Et2O/petroleum ether firstly gave foreruns
  5. washfurther elution with 1-10% Et2O/petroleum ether

Sources & evidence

ORD record
ord-0f3a78e55fa8479c8b33fcaf4da5f798
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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