Réaction #502130

Équation de réaction

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

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

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

→

title compound

Rendement 70.0%

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

Rendement 70.0%

Solvants

CH2Cl2

DMF

Conditions de réaction

Traitement

1. 1
   Autrepartitioned between CH2Cl2 and HCl (1N)
2. 2
   LavageThe aqueous layer was washed with CH2Cl2
3. 3
   Lavagethe combined organic extracts were washed with water, brine
4. 4
   Séchagedried over magnesium sulfate
5. 5
   Concentrationconcentrated in vacuo
6. 6
   AutreThe residue was purified by column chromatography on silica gel eluting with EtOAC/hexane (1:1)

Mode opératoire

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+).

Source