반응 #502124

ord-a3bf16d0509b4b248c7bf161c04f728d

반응 방정식

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
수율 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
수율 79.1%

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The reaction mixture was evaporated to dryness under vacuum
  2. 2
    기타the residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
  3. 3
    세척The organic layer was washed with water, brine
  4. 4
    건조dried over Na2SO4
  5. 5
    여과filtered
  6. 6
    농축concentrated
  7. 7
    기타The product was separated by silica gel column chromatography
  8. 8
    세척eluting with EtOAc/hexane (1:1, Rf=0.15)
  9. 9
    기타recrystalized from ethyl ether and hexane

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08088762B2uspto-grants-2012_01