Reaction #502130

Reaction equation

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

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

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

→

title compound

Yield 70.0%

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

Yield 70.0%

Solvents

CH2Cl2

DMF

Conditions

Workup

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

Procedure

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