Reaction #502124

Reaction equation

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

hydroquinone bis(2-hydroxyethyl)ether

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

NEt3

→

title compound

Yield 79.1%

2-(4-(2-Hydroxyethoxy)phenoxy)ethyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Yield 79.1%

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe reaction mixture was evaporated to dryness under vacuum
2. 2
   Otherthe residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
3. 3
   WashThe organic layer was washed with water, brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   OtherThe product was separated by silica gel column chromatography
8. 8
   Washeluting with EtOAc/hexane (1:1, Rf=0.15)
9. 9
   Otherrecrystalized from ethyl ether and hexane

Procedure

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.27 g, 18.5 mmol), hydroquinone bis(2-hydroxyethyl)ether (10.6 g, 53.3 mmol), N,N-dimethylaminopyridine (DMAP, 2.71 g, 22.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (9.34 g, 48.7 mmol) and NEt3 (13 mL, 93.3 mmol) in DMF (100 mL) was stirred at ambient temperature overnight. The reaction mixture was evaporated to dryness under vacuum and the residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL). The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated. The product was separated by silica gel column chromatography eluting with EtOAc/hexane (1:1, Rf=0.15) and then recrystalized from ethyl ether and hexane to give the title compound as a white solid (6.01 g, 31% yield). Mp 76-78° C. 1H NMR (CDCl3) δ 7.7-7.64 (m, 3H), 7.42-7.38 (m, 1H), 7.15-7.08 (m, 2H), 6.74-6.72 (m 4H), 4.45-4.36 (m, 2H), 4.1-3.85 (m, 7H), 3.90 (s, 3H), 2.13 (br. t, 1H), 1.58 (d, J=7.2 Hz, 3H). 13C NMR (CDCl3) δ 174.6, 157.5, 153.0, 152.8, 135.4, 133.6, 129.2, 128.8, 127.1, 126.1, 125.9, 118.8, 115.7, 115.3, 105.5, 69.7, 66.6, 63.1, 61.4, 55.2, 45.2, 18.4. MS(API) m/z 428 (M+NH4)+. Anal. calcd. for C24H26O6: C, 70.23; H, 6.38. Found: C, 70.01; H, 6.39.

Source