反应详情

To a solution of compound 24A (520 mg, 1.7 mmol) and N-Boc-2(S)-piperidinecarboxylic acid (8A) (584 mg, 2.55 mmol) in anhydrous dichloromethane (30 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 0.4 mL, 2.55 mmol). The reaction mixture was stirred at rt overnight. The solvent was removed. To the residua were added THF (40 mL) and methanol (40 mL) and a solution of LiOH.H2O (2.0 g, 47.68 mmol) in water (20 mL). The mixture was stirred at rt for 3 h. It was then neutralized with acetic acid (3 mL, 52.41 mmol). The mixture was diluted with ethyl acetate (˜100 mL), washed with brine, and dried over sodium sulfate. It was filtered, concentrated and filtered again to remove diisopropylurea. The filtrate was purified with silica column chromatography eluting with hexanes/ethyl acetate (v/v 2/1, 3/2, 1/1) to provide the title compound (25A, 500 mg) as a yellowish solid in 57.2% yield. 1H NMR (CDCl3, 500 MHz) δ 10.62 (br s, 1H), 8.71 (d, 1H, J=2.0 Hz), 8.35 (br s, 1H), 7.84 (s, 1H), 7.55 (s, 4H), 7.22 (dd, 1H, J=9.0, 2.0 Hz), 6.99 (d, 1H, J=9.0 Hz), 4.90 (s, 1H), 4.05 (m, 1H), 2.90 (t, 1H, J=11.5 Hz), 2.35 (m, 1H), 1.80-1.30 (m, 16H). LCMS (ESI) m/z 587.15 (MNa+), 521.05 (MH+), 421.06; HPLC: tR=5.32 min.

1. customThe solvent was removed
2. additionTo the residua were added THF (40 mL) and methanol (40 mL)
3. stirringThe mixture was stirred at rt for 3 h
4. washwashed with brine
5. dry with materialdried over sodium sulfate
6. filtrationIt was filtered
7. concentrationconcentrated
8. filtrationfiltered again
9. customto remove diisopropylurea
10. customThe filtrate was purified with silica column chromatography
11. washeluting with hexanes/ethyl acetate (v/v 2/1, 3/2, 1/1)