Dichloromethane → 4-Chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine

Temperatur

80 °C

A solution of 4,6-dichloro-pyridin-2-ylamine (1.00 g, 6.14 mmol) in DME (75 mL) and water (50 mL) was treated with Cs2CO3 (6.00 g, 18.4 mmol) and 2-(trifluoromethyl)phenylboronic acid (1.52 g, 7.98 mmol). The resulting mixture was degassed by heating under a stream of Ar. Cl2Pd(dppf).DCM (270 mg, 0.368 mmol) was added, and the mixture was heated to 80° C. for 24 h. The cooled mixture was diluted with EtOAc (70 mL) and washed twice with water (50 mL). The combined aqueous layers were extracted twice with EtOAc (50 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 115-g SEPRA Si 35 SPE silica column (Flow rate=30 mL/min; Eluent=EtOAc-hexanes, 1:19 for 15 min, 1:19 to 1:3 over 40 min, then 1:3 until product eluted) to yield 4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine as an off-white solid. 1H-NMR (400 MHz, CDCl3) δ: 7.74 (d, J=7.6 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.50 (t, J=7.7 Hz, 1H), 7.45 (d, J=7.6 Hz, 1H), 6.77 (d, J=1.5 Hz, 1H), 6.53 (d, J=1.5 Hz, 1H), 4.59 (br. s., 2H). Mass Spectrum (LCMS, ESI pos.): Calculated for C12H8N2ClF3: 273.0 (M+H); Measured: 273.0.

1. customThe resulting mixture was degassed
2. temperatureby heating under a stream of Ar
3. washwashed twice with water (50 mL)
4. extractionThe combined aqueous layers were extracted twice with EtOAc (50 mL)
5. dry with materialThe combined organic extracts were dried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified on a 115-g SEPRA Si 35 SPE silica column (Flow rate=30 mL/min
8. wait1:19 to 1:3 over 40 min
9. wash1:3 until product eluted)

ORD-Eintrag

ord-364b31268d6047c5bef46679d45ce298

Quelldatensatz

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09023846B2