Ethyl bromoacetate → Ethyl 2-(4,6-dimethyl-5-nitropyrimidine-2-yloxy)acetate

Temperature

50 °C

Compound 1 (111.86 g) and potassium carbonate (274.21 g: 3 eq.) were suspended in acetone (2 L) and ethyl bromoacetate (165.67 g: 1.5 eq.) was added at room temperature (20 to 30° C.). The equipment used to add ethyl bromoacetate was thoroughly washed with acetone (237 mL) and stirred at 50° C. for 8 hours. Subsequently, the mixture was cooled to 35° C. and was concentrated under reduced pressure. To the resulting residue, toluene (1120 mL) was added and the mixture was stirred at room temperature overnight. The mixture was then suction-filtered and the filtered product was washed with toluene (560 mL). The filtered product was crushed and washed again with toluene (450 mL). The filtrate was evaporated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=1:0 to 4:1) to give 75.98 g (45% yield) of the desired product as a yellow solid.

1. washwas thoroughly washed with acetone (237 mL)
2. temperatureSubsequently, the mixture was cooled to 35° C.
3. concentrationwas concentrated under reduced pressure
4. additionTo the resulting residue, toluene (1120 mL) was added
5. stirringthe mixture was stirred at room temperature overnight
6. filtrationThe mixture was then suction-filtered
7. washthe filtered product was washed with toluene (560 mL)
8. customThe filtered product was crushed
9. washwashed again with toluene (450 mL)
10. customThe filtrate was evaporated under reduced pressure
11. customthe resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=1:0 to 4:1)

ORD record

ord-636d32e0b8414edebfcff8a06c37854d

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592435B2