Acetic Acid → 2-(2,2-Dimethoxyethoxy)-4-ethoxypyrimidine

HRID 1108437Notes

Reaction equation

HRID 1108437 reaction equation
[H-].[Na+].[CH3:3][O:4][CH:5]([O:8][CH3:9])[CH2:6][OH:7].Cl[C:11]1[N:16]=[C:15]([O:17][CH2:18][CH3:19])[CH:14]=[CH:13][N:12]=1.CC(O)=O>CN(C=O)C>[CH3:3][O:4][CH:5]([O:8][CH3:9])[CH2:6][O:7][C:11]1[N:16]=[C:15]([O:17][CH2:18][CH3:19])[CH:14]=[CH:13][N:12]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 5423812,2-DimethoxyethanolHCID 47372802-Chloro-4-ethoxypyrimidine

Product 1

HCID 221323242-(2,2-Dimethoxyethoxy)-4-ethoxypyrimidineYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 60% NaH/mineral oil (2.55 g, 63.96 mmol) in anhydrous DMF (70 mL) at 0° C. under nitrogen atmosphere was slowly added glycolaldehyde dimethyl acetal (Aldrich, 5.65 g, 53.3 mmol). The mixture was stirred at ambient temperature for 1 hour and then transferred to a solution of the product from step (a) (8.05 g, 50.76 mmol) in anhydrous DMF (70 mL) at -55° C. over 15 minutes. The mixture was allowed to warm to -20° C. over 2 hours and then neutralized with AcOH. Solvent was evaporated in vacuo and the residue partitioned between H2O and CH2Cl2. The aqueous phase was extracted with CH2Cl2 and the combined organic phase was dried (Na2SO4) and evaporated in vacuo. The residue was flash chromatographed (EtOAc/hexanes, 1:4) to give the desired product (7.92 g, 69%) as a colourless oil: 1H NMR (CDCl3): δ 1.37 (t, J=7.0 Hz, 3H), 3.44 (s, 6H), 4.36-4.43 (m, 4H), 4.78 (t, J=5.0 Hz, 1H), 6.34 (d, J=6.0 Hz, 1H), 8.15 (d, J=6.0 Hz, 1H); MS m/z229 (M=1, 13%), 197 (100%). Anal Calcd. for C10H16N2O4 : C, 52.62; H, 7.07; N, 12.27. Found: C, 52.45; H, 7.01; N, 12.26.

Workup

  1. temperatureto warm to -20° C. over 2 hours
  2. customSolvent was evaporated in vacuo
  3. customthe residue partitioned between H2O and CH2Cl2
  4. extractionThe aqueous phase was extracted with CH2Cl2
  5. dry with materialthe combined organic phase was dried (Na2SO4)
  6. customevaporated in vacuo
  7. customchromatographed (EtOAc/hexanes, 1:4)

Sources & evidence

ORD record
ord-be931b801b5f4aa8818f265b76b45b1c
Source dataset
uspto-grants-2000_05
Patent number
US06066733

Reaction notes

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