4,6-Dichloropyrimidine → 4-Chloro-6-(2-methoxy-4-nitrophenyl)pyrimidine

온도

80 °C

2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2 g, 7.17 mmol) was dissolved in 20 ml of EtOH and the resulting solution was concentrated to ˜15 ml and diluted with EtOH (30 ml). To this solution was added 4,6-dichloropyrimidine (1.495 g, 10.03 mmol), Bis(triphenylphosphine)palladium(II) chloride (0.075 g, 0.107 mmol) and aqueous potassium hydrogenbicarbonate (2.152 g, 21.50 mmol) (in 10 ml of water) at rt. The resulting mixture was stirred at 80° C. for 2 h. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc/aqueous sodium bicarbonate. The aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml), dried over magnesium sulfate, filtered and concentrated. The residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜30%) to get 0.66 g (35%) of product as white solid. LC-MS (M+H)+=266.1. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 3H) 7.90 (d, J=2.26 Hz, 1H) 7.98 (dd, J=8.53, 2.26 Hz, 1H) 8.09 (d, J=1.00 Hz, 1H) 8.26 (d, J=8.53 Hz, 1H) 9.10 (d, J=1.25 Hz, 1H).

1. concentrationthe resulting solution was concentrated to ˜15 ml
2. additiondiluted with EtOH (30 ml)
3. concentrationThe reaction was concentrated under vacuum
4. customThe residue was partitioned between EtOAc/aqueous sodium bicarbonate
5. extractionThe aqueous layer was extracted with EtOAc (3×20 ml)
6. washThe combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜30%)

ORD 기록

ord-a3113bde5d6c416ea34c0528ec749778

출처 데이터셋

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08637525B2