Water → Methyl 2-methoxy-6-(pyrimidin-2-yl)benzoate

Temperature

80 °C

In a microwave vial was dissolved methyl 2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (500 mg, 1.71 mmol), commercially available from Combi-Blocks (CAS #1146214-77-8), and 2-bromopyrimidine (344 mg, 2.05 mmol) in THF (8.5 mL). Na2CO3 (544 mg, 5.14 mmol) was then added followed by water (4 mL) and the reaction mixture was degassed with N2 for 10 minutes. PdCl2(dtbpf) (45 mg, 0.069 mmol) was then added and the reaction mixture was heated at 80° C. for 4 h. The mixture was cooled to room temperature and water and EtOAc added. The reaction mixture was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude was purified via silica gel chromatography (0-70% EtOAc in hexanes) to afford the title compound (265 mg, 63%). MS (ESI) mass calcd. for C13H12N2O3, 244.1; m/z found 245.1 [M+H]+. 1H NMR (400 MHz, Chloroform-d) 8.78 (d, J=4.9 Hz, 2H), 7.99 (dd, J=7.9, 0.9 Hz, 1H), 7.49 (t, J=8.1 Hz, 1H), 7.19 (t, J=4.8 Hz, 1H), 7.09 (dd, J=8.3, 0.9 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H).

1. customthe reaction mixture was degassed with N2 for 10 minutes
2. temperatureThe mixture was cooled to room temperature
3. extractionThe reaction mixture was extracted with EtOAc (3×)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude was purified via silica gel chromatography (0-70% EtOAc in hexanes)

ORD record

ord-4c2338daf6ba4e78807337f637807b27

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062078B2