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

HRID 414926

반응식

HRID 414926 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-59628f3e3a754912acca6d943aa966b4
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088762B2

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