Methanol → Methyl 3-oxo-3-(pyrimidin-5-yl)propanoate

Temperature

85 °C

Add a 25 wt % solution of sodium methoxide in methanol (4.5 mL, 19.8 mmol) to toluene (40 mL) and heat to 85° C. under N2. Dissolve pyrimidine-5-carboxylic acid ethyl ester (2.0 g, 13.2 mmol) in EtOAc (2.1 mL) and add dropwise to the toluene solution. Heat the reaction mixture for 1 h, then add a suspension of sodium methoxide (715 mg, 13.2 mmol) in EtOAc (15 mL) dropwise. Heat the reaction mixture at 85° C. overnight, then cool to RT and pour into a solution of glacial acetic acid (12 mL) and water. (50 mL). After stirring for 1 h at RT, extract with EtOAc (3×100 mL). Wash the organic phase with brine (200 mL), dry over sodium sulfate, filter, and concentrate under reduced pressure to give the title compound as a mixture of tautomers: 1H NMR (300 MHz, CDCl3) enol form δ 12.43 (s, 1H), 9.26 (s, 1H), 9.10 (s, 2H), 5.76 (s, 1H), 3.86 (s, 3H); keto form δ 9.42 (s, 1H), 9.30 (s, 2H), 4.06 (s, 3H), 3.74 (s, 2H).

1. temperatureHeat the reaction mixture for 1 h
2. additionadd
3. temperatureHeat the reaction mixture at 85° C. overnight
4. temperaturecool to RT
5. extractionextract with EtOAc (3×100 mL)
6. washWash the organic phase with brine (200 mL)
7. dry with materialdry over sodium sulfate
8. filtrationfilter
9. concentrationconcentrate under reduced pressure

ORD record

ord-3f42848dedde40eebb02442a32d6da2b

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179804B2