反応 #502130

反応方程式

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid

N,N-bis(2-hydroxyethyl)-p-toluenesulfonamide

1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride

→

title compound

収率 70.0%

2-((2-Hydroxyethyl)((4-methylphenyl)sulfonyl)amino)ethyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

収率 70.0%

溶媒

CH2Cl2

DMF

反応条件

後処理

1. 1
   その他partitioned between CH2Cl2 and HCl (1N)
2. 2
   洗浄The aqueous layer was washed with CH2Cl2
3. 3
   洗浄the combined organic extracts were washed with water, brine
4. 4
   乾燥dried over magnesium sulfate
5. 5
   濃縮concentrated in vacuo
6. 6
   その他The residue was purified by column chromatography on silica gel eluting with EtOAC/hexane (1:1)

実験手順

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid(naproxen, 5.0 g, 21.7 mmol), N,N-bis(2-hydroxyethyl)-p-toluenesulfonamide (16.89 g, 65.1 mmol) and N,N-dimethylaminopyridine (DMAP, 0.530 g, 4.34 mmol) in CH2Cl2 (250 mL) and DMF (3 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 4.99 g, 26.05 mmol). The reaction mixture was stirred overnight at room temperature, and then partitioned between CH2Cl2 and HCl (1N). The aqueous layer was washed with CH2Cl2 and the combined organic extracts were washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with EtOAC/hexane (1:1) to give the title compound as a thick oil (7.15 g, 15.16 mmol, 70% yield): 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J=8.6 Hz, 2H), 7.66 (m, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.40 (dd, J=1.7, 8.5 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 7.18 (dd, J=2.5, 8.8 Hz, 1H), 7.14 (d, J=2.4 Hz, 1H), 4.28 (m, 2H), 3.95 (s, 3H), 3.88 (q, J=7.2 Hz, 1H), 3.38 (m, 2H), 3.09 (t, J=5.1 Hz, 2H), 2.44 (s, 3H), 2.18 (t, J=6.0 Hz, 1H), 1.61 (d, J=7.2 Hz, 3H). Mass spectrum (API-TIS) m/z 472 (MH+), 489 (M+18+).

出典