反应详情

To a cold solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-methoxymethyl-piperazine-1-yl}-3-naphthalen-2-yl-propionic acid, 64, (2.7 g, 4.3 mmol) and PyBOP (2.9 g, 5.6 mmol) in anhydrous dichloromethane (15 mL) is added 2M methyl amine solution in THF (4.4 mL, 8.8 mmol) and triethyl amine (1.5 mL, 10.7 mmol). The reaction mixture is placed in a refrigerator overnight. EtOAc (50 mL) and water (200 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×100 mL). All organic layers are combined and washed with brine (100 mL), and dried over Na2SO4. The solution is concentrated in vacuo to afford 2.6 g (100% yield) of the desired product. 1H NMR (CDCl3, δ): 7.62–7.50 (m, 3H), 7.45 (s, 1H), 7.35–7.12 (m, 3H), 7.05–6.92 (m, 2H), 6.82–6.70 (m, 2H), 5.45 (dd, J=20.5, 8.2 Hz, 0.5H), 4.75–4.45 (m, 1H), 4.05 (d, J=12.3 Hz, 0.5H), 3.5–3.20 (m, 1H), 3.20–3.08 (m, 1H), 3.08–2.98 (m, 1H), 2.92 (s, 8H), 2.84–2.64 (m, 2H), 2.55 (br s, 2H), 2.40–1.85 (m, 1H), 1.6 (s, 7H), 1.22 (d, J=6.6 Hz, 7H); 13C NMR, δ 171.6, 171.4, 171.2, 170.2, 163.5, 160.3, 154.9, 137.3,137.2, 132.6, 132.3, 132.1, 131.2, 127.6, 127.5, 126.0, 125.4, 115.4, 115.1, 114.9, 79.5, 79.3, 70.2, 69.6, 69.3, 58.9, 58.8, 53.3, 51.2, 49.8, 49.6, 48.7, 48.3, 46.3, 42.9, 39.8, 38.9, 38.6, 33.6, 28.3, 26.5, 26.4, 25.8, 25.7.

1. customis placed in a refrigerator overnight
2. customthe organic layer is separated
3. extractionThe aqueous layer is extracted with EtOAc (3×100 mL)
4. washwashed with brine (100 mL)
5. dry with materialdried over Na2SO4
6. concentrationThe solution is concentrated in vacuo