1,2-Dichloroethane → (S)-tert-Butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Participants

Reaction Steps

To a 0° C. solution of (S)-2-(tert-butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.32 g, 4.49 mmol) in DMF (30 mL) was added EDC (1.03 g, 5.39 mmol) followed by HOAt (0.73 g, 5.39 mmol). After 10 min, (R)-1,2,3,4-tetrahydronaphthalen-1-amine (Alfa Aesar, 0.66 mL, 4.49 mmol) and NMM (1.48 mL, 13.5 mmol) were added. The resulting reaction mixture was allowed to warm to room temperature over 4 h and then poured into a separatory funnel containing EtOAc and sat. aq. NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×), and the combined organic extracts were washed with 1N HCl, 10% LiCl and sat. NaCl and then dried over MgSO4, filtered and concentrated in vacuo. The crude oil was then purified by flash chromatography (gradient elution from 0 to 70% EtOAc/hexanes) to afford the title compound (1.25 g, 2.96 mmol, 66% over 3 steps) as a light yellow foam. 1H NMR (CDCl3) δ 7.18-6.86 (m, 4H), 6.84-6.67 (m, 1H), 6.58-6.39 (m, 1H), 6.04-5.74 (m, 2H), 4.94 (d, J=5.7 Hz, 1H), 4.78-4.61 (m, 1H), 4.56-4.41 (m, 1H), 4.20 (d, J=15.6 Hz, 1H), 3.34 (d, J=13.4 Hz, 1H), 3.02 (d, J=12.1 Hz, 1H), 2.81-2.60 (m, 2H), 1.87-1.68 (m, 2H), 1.67-1.54 (m, 2H), 1.53-1.37 (m, 9H); MS (ESI+) m/z 423.2 (M+H)+.

Provenance & Evidence