Dimethylformamide → (R)-N,N-Diisopropyl-3-(2-benzyloxy-5-formylphenyl)-3-phenylpropanamine

Participants

Reaction Steps

n-BuLi (2.5 M in hexane, 19 mL, 47.5 nmol) was added to a solution of to (R)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropanamine (prepared as described in WO 94/11337, Example 1) (8.9 g, 18.52 mmol) in dry diethyl ether (100 mL) kept at −40° C. under nitrogen atmosphere. After 1.5 hour of stirring, additional n-BuLi (10 mL, 25 mmol) was added and after 2 hours another n-BuLi (5 mL, 12.5 mmol) was added. The reaction was then stirred for 15 minutes and DMF (6 mL, 77.8 mmol) was added followed by additional DMF (5 mL, 64.8 mmol) after 20 minutes of stirring. The temperature was allowed to rise to room temperature and after 35 minutes of stirring, NH4Cl (sat.) was added followed by water and diethyl ether. The layers were separated and the aqueous layer was extracted with diethyl ether. The combined organic layers were dried (MgSO4) and the solvent was evaporated. The residue was chromatographed on silica (toluene-triethylamine 90:10) to afford 8 g (100%) of a yellowish oil; 1H NMR (CDCl3) δ0.90 (m, 12H), 2.12-2.40 (m, 4H), 2.95 (m, 2H), 4.44 (t, 1H), 5.10 (s, 2H), 6.95 (d, 1H), 7.15-7.36 (m, 10H), 7.70 (dd, 1H), 7.91 (s, 1H), 9.88 (s, 1H).

Provenance & Evidence