[1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) Dichloride Dichloromethane Adduct

Used Chemicals

• 2-Bromo-3-methylpyridine [B1894]
• 3-(tert-Butoxycarbonyl)phenylboronic Acid [B4726]
• [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) Dichloride Dichloromethane Adduct [B2064]
• K₂CO₃ [P1748]
• Toluene
• Water

Procedure

To a solution of 2-bromo-3-methylpyridine (103 mg, 60 mmol) in degassed toluene (0.6 mL, 0.1 mol/L) and H₂O (0.2 mL) was added 3-(tert-butoxycarbonyl)phenylboronic acid (150 mg, 0.66 mmol, 1.1 equiv), K₂CO₃ (398 mg, 2.9 mmol, 4.8 equiv), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (24.5 mg, 3.0 μmol, 5.0 mol%) and the mixture was stirred at reflux for 4 h. The reaction mixture was diluted with H₂O (10 mL) and extracted with EtOAc (20 mL x 3). The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (hexane : EtOAc = 1 : 0 to 4 : 1) to give 1 as a pale yellow oil (155 mg, 94%).

Experimenter’s Comments

The reaction mixture was monitored by TLC (hexane : EtOAc = 2 : 1, Rf = 0.62).

Analytical Data（Compound 1）

¹H NMR (400 MHz, CDCl₃); δ 8.54 (brd, J = 5.0 Hz, 1H), 8.14 (q, J = 1.5 Hz, 1H), 8.03 (dt, J = 7.8, 1.4 Hz, 1H), 7.69 (dq, J = 7.6, 1.5 Hz, 1H), 7.60 (m, 1H), 7.51 (dt, J = 7.7, 1.1 Hz, 1H), 7.21 (dd, J = 7.8, 4.6 Hz, 1H), 2.36 (s, 3H), 1.58 (s, 9H).

Lead Reference

• Evaluation of 1,2,3-Triazoles as Amide Bioisosteres In Cystic Fibrosis Transmembrane Conductance Regulator Modulators VX-770 and VX-809
• J. E. Doiron, C. A. Le, B. K. Ody, J. B. Brace, S. J. Post, N. L. Thacker, H. M. Hill, G. W. Breton, M. J. Mulder, S. Chang, T. M. Bridges, L. Tang, W. Wang, S. M. Rowe, S. G. Aller, M. Turlington. Chem. Eur. J. 2019, 25, 3662.

References

• S. Iimura, W. Wu, Tetrahedron Lett. 2010, 51, 1353.