تفاعل #502124

ord-a3bf16d0509b4b248c7bf161c04f728d

معادلة التفاعل

COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
(2S)-2-(6-methoxy(2-naphthyl))propanoic acid
OCCOc1ccc(OCCO)cc1
hydroquinone bis(2-hydroxyethyl)ether
CCN=C=NCCCN(C)C.Cl
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
CCN(CC)CC
NEt3
COc1ccc2cc([C@H](C)C(=O)OCCOc3ccc(OCCO)cc3)ccc2c1
title compound
المردود 79.1%
COc1ccc2cc([C@H](C)C(=O)OCCOc3ccc(OCCO)cc3)ccc2c1
2-(4-(2-Hydroxyethoxy)phenoxy)ethyl(2S)-2-(6-methoxy(2-naphthyl))propanoate
المردود 79.1%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىThe reaction mixture was evaporated to dryness under vacuum
  2. 2
    أخرىthe residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
  3. 3
    غسيلThe organic layer was washed with water, brine
  4. 4
    تجفيفdried over Na2SO4
  5. 5
    ترشيحfiltered
  6. 6
    تركيزconcentrated
  7. 7
    أخرىThe product was separated by silica gel column chromatography
  8. 8
    غسيلeluting with EtOAc/hexane (1:1, Rf=0.15)
  9. 9
    أخرىrecrystalized from ethyl ether and hexane

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08088762B2uspto-grants-2012_01