Diisopropylethylamine → (S)-N-(2-fluoro-5-(trifluoromethyl)benzyl)-2-phenylbutanamide

Participants

Reaction Steps

A solution of (S)-2-phenylbutanoic acid (1-d, 50 mg, 0.30 mmol, Sigma-Aldrich, Milwaukee, Wis.) and diisopropylethylamine (98 uL, 0.60 mmol) in N,N-dimethylformamide (1 mL) was treated at room temperature with benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 158 mg, 0.30 mmol). After 15 min, (2-fluoro-5-(trifluoromethyl)phenyl)methanamine (1-g, 60 mg, 0.30 mmol, Synthesis, Inc., Wyndham, N.H.) was added. The reaction mixture was stirred for 3 h, partitioned between dichloromethane and 0.5N—NaOH. The aqueous layer was removed and the organic layer washed with 0.5N—HCl. The aqueous layer was removed by filtering through a plastic frit. The organic layer was concentrated in vacuo to give the desired product (1-1); HRMS (M+1)=340.129; 1H NMR (500 MHz, CDCl3) δ7.49 (bs, 1 H), 7.41 (d, 1 H, J=6.5 Hz), 7.34-7.26 (m, 5 H), 7.10 (t, 1 H, J=9.0 Hz), 5.77 (bs, 1 H), 4.47 (d, 1 H, J=3.0 Hz), 3.30 (t, 2 H, J=7.5 Hz), 2.22 (m, 1 H), 1.82 (m, 1 H), 0.89 (t, 3 H, J=7.5 Hz).

Provenance & Evidence