Benzyl Bromide → (S)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene

Participants

Reaction Steps

To a solution of 1-fluoro-3-((4-fluorophenyl)(isocyano)methyl)-5-(trifluoromethyl)benzene (234 mg, 0.79 mmol) in toluene (8 mL) was added tetrabutylammonium bromide (75 mg, 0.23 mmol) and benzyl bromide (0.185 mL, 1.56 mmol) followed by 50% KOH(aq) (2.5 mL). The reaction mixture was vigorously stirred for 3 minutes. The reaction mixture was transferred to a separatory funnel and washed with H2O (2.5 mL). The organic fraction was dried over Na2SO4, filtered through a pad of basic alumina and concentrated under reduced pressure. The residue was purified by chiral prep HPLC (Chiralcel OD-H column, 20×250 mm isocratic elution with isopropyl alcohol (10%) and heptane, 20 mL/min, monitoring at 254 nm) to give (R)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene (RT=6.2 minutes, 128 mg, 42% yield) and (S)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene (RT=7.8 minutes, 128 mg, 42% yield) as clear colorless oils. LCMS: RT=1.94 min [M−NC] 361.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% acetonitrile/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) δ ppm 3.61 (d, J=13.18 Hz, 1H), 3.67 (d, J=13.18 Hz, 1H), 6.83 (d, J=7.47 Hz, 2H), 7.08 (t, J=8.57 Hz, 2H), 7.17-7.34 (m, 8H).

Provenance & Evidence