Tris(1,1-dimethylethyl)phosphine → tert-Butyl-4-(7-amino-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of Pd2(dba)3 (0.107 g, 0.1172 mmol) in dry THF (5 mL) was treated with PtBu3 (10% in Hexanes, 1.42 mL, 0.4688 mmol). The mixture was then treated with compound 3 (0.9594 g, 2.344 mmol) in dry THF (15 mL) and LiHMDS (4.69 mL, 4.688 mmol) at room temperature. The solution was stirred at 100° C. for 3 hours. At room temperature, the solution was quenched with 1M TBAF in THF solution (5 mL) and was stirred for 20 minutes. The reaction was the diluted with 3N NaOH solution (50 mL) and was extracted with ethyl acetate (150 mL). The organic layer was dried (Na2SO4) and was concentrated. The crude product was subject to flash chromatography on silica gel using 2.5% 2M NH3 methanol/CH2Cl2, which resulted in a dark brown foam, compound 4 (0.691 g, 85%). 1H NMR (CDCl3) δ 6.79 (d, J=5.1 Hz, 1H), 6.51-6.44 (m, 2H), 4.06-4.03 (m, 2H), 3.56-3.51 (m, 1H), 3.28 (tt, J=7.2, 21.3 Hz, 1H), 2.92-2.77 (m, 4H), 2.68-2.64 (m, 2H), 1.82 (d, J=11.1 Hz, 2H), 1.66-1.40 (m, 7H), 1.36 (s, 9H).

Provenance & Evidence