反应详情

To a solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester, 15, (531 mg, 0.842 mmol) in a mixture of THF (5 mL)/CH3OH (1 mL)/H2O (2 mL) is added LiOH (100 mg, 4.17 mmol). The reaction mixture is stirred for 4 hours, acidified with 1N HCl to pH 3 and extracted several times with EtOAc. The combined extracts are dried over Na2SO4, filtered, concentrated in vacuo and dried under high vacuum to give the free acid in quantitative yield, which is used directly without further purification. 1H NMR (300 MHz, CD3OD, Rotamers) δ 7.72–7.87 (m, 3H), 7.68 (s, 1H), 7.37–7.53 (m, 3H), 7.12–7.28 (m, 2H), 6.99–7.06 (m, 2H), 5.54–5.66 (m, 1H), 4.52–4.80 (m, 1.5H), 3.82–4.38 (m, 1.5H), 3.18–3.64 (m, 4H), 2.70–3.02 (m, 3H), 0.80–1.43 (m, 11H), −0.78–0.10 (m, 5H); 13C NMR (75 MHz, CD3OD, Rotamers) δ 171.68, 171.58, 170.23, 169.29, 167.86, 163.70, 156.08, 134.69, 134.57, 133.71, 133.14, 132.70, 131.26, 131.15, 130.73, 130.64, 128.19, 128.12, 127.55, 127.38, 127.29, 127.07, 126.12, 125.64, 79.61, 79.34, 58.68, 57.04, 56.18, 52.13, 51.65, 43.21, 42.29, 41.29, 38.61, 37.32, 37.21, 36.27, 34.23, 33.93, 27.50, 27.41, 6.45, 3.92, 3.66, 3.33; MS (ESMS) m/z 618.2 (M+H)+.

1. extractionextracted several times with EtOAc
2. dry with materialThe combined extracts are dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customdried under high vacuum
6. customto give the free acid in quantitative yield, which
7. customis used directly without further purification