Potassium Hydroxide → (S)-(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

Participants

Reaction Steps

A mixture of [IrHCl2(COD)]2 (54.4 mg, 0.073 mmol) and (1R,2R)—N,N′-bis[2-(diphenylphosphino)benzyl]cyclohexane-1,2-diamine (44.8 mg, 0.067 mmol) in isopropanol was stirred at room temperature for 30 minutes. A solution of (2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanone in isopropanol was added to mixture followed by potassium hydroxide (44.8 mg, 0.799 mmol) and stirred at room temperature for 18 hours. Isopropanol was removed in vacuo and the crude product was purified on Biotage 40+M silica column, eluted with 0-30% ethyl acetate in heptane, to afford 3.7 g (92%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 0.92-1.17 (m, 5H) 1.24 (d, J=15.77 Hz, 1H) 1.54-1.60 (m, 1H) 1.61-1.67 (m, J=2.07 Hz, 2H) 1.73-1.79 (m, 1H) 1.93 (d, J=12.86 Hz, 1H) 2.25 (s, 1H) 4.20 (s, 3H) 4.65 (d, J=7.05 Hz, 1H) 4.70 (d, J=15.77 Hz, 1H) 4.76 (t, J=15.35 Hz, 2H) 4.86 (d, J=15.77 Hz, 1H) 7.34 (s, 1H) 7.50-7.59 (m, 2H) 7.65 (s, 2H) 7.77 (s, 1H). MS (ES+) Calc: 595.2, Found: 596.5 (M+1). 95.9% ee determined by chiral HPLC on Chiralpak AD-H (4.6 mm×25 cm) eluted at 6.912 min using 90/10 heptane/IPO (1 mL/min).

Provenance & Evidence