4-chloro-5-Methyl-5,7-dihydrofuro[3,4-d]pyriMidine synthesis

Yield:1000984-97-3 96%

Reaction Conditions:

with trichlorophosphate in acetonitrile; for 3 h;Heating / reflux;

Steps:

1.3

Step 3: To a suspension of 5-methyl-5,7-dihydrofuro[3,4-^]pyrimidin-4-ol (1.2 g,7.9 mmol) in acetonitrile (50 mL) was added via syringe POCl₃ (3.6 g, 23.7 mmol) and the mixture heated to reflux for 3 hours. The mixture was allowed to cool to room temperature and then concentrated. The residue was diluted with EtOAc and quenched by pouring into saturated NaHCO₃. The organic layer was separated and the aqueous layer extracted with EtOAc (3 x 100 mL). The combined organic layers were dried (MgSO₄) and concentrated to give 4-chloro-5- methyl-5,7-dihydrofuro[3,4-J]pyrimidine (1.3 g, 96%) as a light brown oil which was used in the next step without further purification. ¹H NMR (CDCl₃, 400 MHz) δ 8.89 (s, IH), 5.46 (q, J = 6.4 Hz, IH), 5.15 (dd, J = 14.4, 2.8 Hz, IH), 5.02 (dd, J = 14.4, 2.8 Hz, IH), 1.62 (d, J = 6.4 Hz, 3H).

References:

WO2008/6025,2008,A1 Location in patent:Page/Page column 60