Reacción #1960817

Ecuación de reacción

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

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

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

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title compound

Rendimiento 70.0%

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

Rendimiento 70.0%

Disolventes

CH2Cl2

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otropartitioned between CH2Cl2 and HCl (1N)
2. 2
   LavadoThe aqueous layer was washed with CH2Cl2
3. 3
   Lavadothe combined organic extracts were washed with water, brine
4. 4
   Secadodried over magnesium sulfate
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   OtroThe residue was purified by column chromatography on silica gel eluting with EtOAC/hexane (1:1)

Procedimiento

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+).

Fuente