反応 #502124

ord-a3bf16d0509b4b248c7bf161c04f728d

反応方程式

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
収率 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
収率 79.1%

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他The reaction mixture was evaporated to dryness under vacuum
  2. 2
    その他the residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
  3. 3
    洗浄The organic layer was washed with water, brine
  4. 4
    乾燥dried over Na2SO4
  5. 5
    ろ過filtered
  6. 6
    濃縮concentrated
  7. 7
    その他The product was separated by silica gel column chromatography
  8. 8
    洗浄eluting with EtOAc/hexane (1:1, Rf=0.15)
  9. 9
    その他recrystalized from ethyl ether and hexane

実験手順

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.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08088762B2uspto-grants-2012_01