Tricyclohexylphosphine → 5-Cyclopropyl-2-methylaniline

Temperature

100 °C

To a mixture of 5-bromo-2-methylaniline (3.51 g), cyclopropylboronic acid monohydrate (2.55 g), tricyclohexylphosphine (about 0.6 mol/L toluene solution, 3.14 mL), tripotassium phosphate monohydrate (15.2 g), toluene (52.4 mL), and water (5.24 mL) was added palladium(II) acetate (212 mg), and this mixture was stirred at 100° C. for 15 hours. The reaction mixture was left to be cooled, and filtrated through a Celite (registered trademark) pad. The pad was washed with ethyl acetate (100 mL). The filtrate and the washing liquid were mixed, and washed with water/saturated brine (1/1). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (2.25 g). 1H-NMR (CDCl3) δ ppm: 0.58-0.67 (2H, m), 0.83-0.93 (2H, m), 1.73-1.84 (1H, m), 2.12 (3H, s), 3.54 (2H, br s), 6.35-6.50 (2H, m), 6.93 (1H, d, J=7.5 Hz).

1. waitThe reaction mixture was left
2. temperatureto be cooled
3. filtrationfiltrated through a Celite (registered trademark) pad
4. washThe pad was washed with ethyl acetate (100 mL)
5. additionThe filtrate and the washing liquid were mixed
6. washwashed with water/saturated brine (1/1)
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

ORD record

ord-6cffc94b45484dffa81f101fddbfef69

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815903B2