反应详情

To 5-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (Ex. 4a, 440 mg, 0.84 mmol) in 5 mL of THF was added LiAlH4 (128 mg, 3.4 mmol) in 4 portions. The mixture was stirred for 2 h at room temperature and then quenched with saturated NH4Cl (30 mL) and extracted with Ethyl acetate (2×3 0 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. Chromatography (10-60% Ethyl acetate/hexanes) gave the title compound as a light-pink solid (195 mg, 47%), mp 64-65° C. 1H NMR (400 MHz, CDCl3): δ 7.27 (s, 2H), 7.07 (d, J=2 Hz, 1H), 6.32 (d, J=2 Hz, 1H), 5.30 (s, 1H), 4.59 (s, 2H), 3.73 (s, 3H), 3.57 (m, 2H), 2.77 (m, 1H), 2.48 (m, 2H), 1.99 (m, 2H), 1.70 (m, 2H), 1.41 (s, 18H). ESI/CI-MS m/z 495 ([M+H]+), 493 ([M−H]−). Three HPLC (reverse-phase, C18) methods were used to determine the purity of the title compound. Method 1: gradient elution, 50% to 99% solvent B (A=aqueous 0.1% H3PO4, B=MeCN) in 15 min. Purity (UV-VIS): 98.7% (215 nm), 97.6% (254 nm), 98.6% (280 nm); Method 2: gradient elution, 40% to 95% solvent B (A=10 mM NH4OAc, B=MeCN) in 6 min. Purity (UV-VIS λ): 98.0% (215 nm), 97.8% (254 nm), 97.8% (280 nm); Method 3: gradient elution, 60% to 85% solvent B (A=aqueous 0.1% H3PO4, B=MeCN) in 15 min. Purity (UV-VIS): 98.3% (238 nm).

1. customquenched with saturated NH4Cl (30 mL)
2. extractionextracted with Ethyl acetate (2×3 0 mL)
3. dry with materialThe combined organic extracts were dried over Na2SO4
4. concentrationconcentrated under reduced pressure