Methyl iodide → 4-(Dimethoxymethyl)-2-(methylsulfanyl)pyrimidine

HRID 1422561Notes

Reaction equation

HRID 1422561 reaction equation
I[CH3:2].[CH3:3][O:4][CH:5]([O:13][CH3:14])[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([S-:12])[N:7]=1.[Na+]>CO>[CH3:14][O:13][CH:5]([O:4][CH3:3])[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([S:12][CH3:2])[N:7]=1

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 20716446HCID 20716446, compound

Product 1

HCID 154070074-(Dimethoxymethyl)-2-(methylsulfanyl)pyrimidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Iodomethane (128 g, 902 mmol, 1.20 equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (2) (156 g, 751 mmol) in methanol (700 mL, 1.1 M) while maintaining the reaction temperature below 28° C. using an ice-water bath for cooling. The resulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layer was concentrated under reduced pressure and the crude residue purified by passing through a short silica gel pad and washing with diethyl ether (200 mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3) as a brown oil (53.7 g, 150 g theoretical, 35.7%). LC-MS m/z 201 (M+1). Reference: WO 2006/0097341A1, pg 67.

Workup

  1. temperaturewhile maintaining the reaction temperature below 28° C.
  2. temperaturefor cooling
  3. customAfter removal of the solvent under reduced pressure
  4. additionthe residue was diluted with water (300 mL)
  5. extractionextracted with ethyl acetate (2×150 mL)
  6. concentrationThe combined organic layer was concentrated under reduced pressure
  7. customthe crude residue purified
  8. washwashing with diethyl ether (200 mL)

Sources & evidence

ORD record
ord-da62b7d81acd46dbb85dd812844ce4c0
Source dataset
uspto-grants-2015_01
Patent number
US08927525B2

Reaction notes

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