1,2-Dimethoxyethane → 2-Fluoro-3-(4-methylpyridin-3-yl)benzonitrile

A reaction flask was charged with tetrakis(triphenylphosphine)palladium(0) (1.040 g, 0.900 mmol), 3-bromo-2-fluorobenzonitrile (3.6 g, 18.00 mmol), sodium carbonate (7.63 g, 72.0 mmol), and 4-methylpyridin-3-ylboronic acid (2.59 g, 18.90 mmol). The mixture was stirred at room temperature for 10 min under N2, then DME (67.2 mL), EtOH (33.6 mL), and water (33.6 mL) were added sequentially. The resultant mixture was heated at 90° C. overnight. After 17 hr, the reaction mixture was allowed to cool to room temperature. The reaction was quenched with water. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a brown residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (120 g column, 85 mL/min, 0-70% EtOAc in hexanes over 25 min, tr=15 min) gave the title compound (2.80 g, 13.19 mmol, 73.3% yield) as a purple residue. ESI MS (M+H)+=213.1. HPLC Peak tr=1.01 minutes. Purity >99%. HPLC Conditions: C.

1. waitAfter 17 hr
2. temperatureto cool to room temperature
3. customThe reaction was quenched with water
4. additionThe reaction mixture was diluted with EtOAc
5. customThe layers were separated
6. extractionthe aqueous phase was extracted with EtOAc (3×)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford a brown residue
11. customto be chromatographed
12. customPurification of the crude material by silica gel chromatography
13. customan ISCO machine (120 g column, 85 mL/min, 0-70% EtOAc in hexanes over 25 min, tr=15 min)

ORD 기록

ord-ca0be192b3bc4851ab98189a75d47ceb

출처 데이터셋

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08969586B2