Thiodiglycol → 2-(2-Hydroxyethylthio)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate

HRID 1514757

反応式

HRID 1514757 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2.[S:18]([CH2:22][CH2:23]O)[CH2:19][CH2:20][OH:21].Cl.CN(C)CCCN=C=NCC.CCOCC.CCCCCC>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([O:16][CH2:23][CH2:22][S:18][CH2:19][CH2:20][OH:21])=[O:15])[CH:7]=[CH:6]2

参加物

6

反応物 4

HCID 5447ThiodiglycolHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21584099Diethylether hexane

生成物 1

HCID 210759292-(2-Hydroxyethylthio)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate収率 81.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 15.0 g, 65 mmol), 2,2′-thiodiethanol (40 g, 325 mmol) and N,N-dimethylaminopyridine (DMAP, 1.59 g, 13 mmol) in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 14.98g, 78 mmol) as a solid, in portions. After stirring for 3 hours at room temperature, TLC analysis indicated the reaction was complete. The reaction mixture was partitioned between CH2Cl2 and water, and the water layer was washed with more CH2Cl2. The combined organic layer was washed with water, 0.1 N HCl, water, brine, and dried over magnesium sulfate. The solution was concentrated under vacuum, and the residue was purified via column chromatography, 5% ethyl acetate/dichloromethane. The appropriate fractions were combined, and the solvent evaporated. Trituration of the residue with ether/hexane gave the title compound as a white solid (17.72 g, 81% yield). Mp 58-61° C. 1H NMR (300 MHz, CDCl3) δ 7.70 (d, J=8.6 Hz, 2H), 7.67 (d, J=0.9 Hz, 1H), 7.40 (dd, J=1.7, 8.5 Hz, 1H), 7.14 (dd, J=2.5, 8.8 Hz, 1H), 7.11 (d, J=2.5 Hz, 1H), 4.24 (t, J=6.7 Hz, 2H), 3.86 (q, J=7.2 Hz, 1H), 3.60 (app q, J=6.0 Hz, 2H), 2.69 (t, J=6.6 Hz, 2H), 2.61 (t, J=5.9 Hz, 2H), 2.00 (t, J=6.2 Hz, 1H), 1.59 (d, J=7.2 Hz, 3H). Mass spectrum (API-TIS) m/z 352 (MNH4+); Anal. calcd. for C18H22O4S: C, 64.65; H, 6.63; S, 9.59; Found: C, 64.62; H, 6.59; S, 9.47.

後処理

  1. customThe reaction mixture was partitioned between CH2Cl2 and water
  2. washthe water layer was washed with more CH2Cl2
  3. washThe combined organic layer was washed with water, 0.1 N HCl, water, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe solution was concentrated under vacuum
  6. customthe residue was purified via column chromatography, 5% ethyl acetate/dichloromethane
  7. customthe solvent evaporated

出典と根拠

ORDレコード
ord-38c5ff091aa14458bcf989705745c5eb
出典データセット
uspto-grants-2012_07
特許番号
US08222277B2

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