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

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 (incorporated by reference), pg 67.

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)

ORD record

ord-5f262d258db84e2db0ad5e20510ee4da

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901145B2