Реакция #502124

Уравнение реакции

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

hydroquinone bis(2-hydroxyethyl)ether

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

NEt3

→

title compound

Выход 79.1%

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

Выход 79.1%

Растворители

DMF

Условия реакции

Обработка

1. 1
   ДругоеThe reaction mixture was evaporated to dryness under vacuum
2. 2
   Другоеthe residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
3. 3
   ПромывкаThe organic layer was washed with water, brine
4. 4
   Сушкаdried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe product was separated by silica gel column chromatography
8. 8
   Промывкаeluting with EtOAc/hexane (1:1, Rf=0.15)
9. 9
   Другоеrecrystalized from ethyl ether and hexane

Методика

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.

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