Naproxen → (2S)-1-(4-Hydroxybutylthio)-2-(6-methoxy(2-naphthyl))propan-1-one

HRID 1873637

반응식

HRID 1873637 반응식
[CH3:1][C@H:2]([C:15]([OH:17])=O)[C:3]1[CH:4]=[CH:5][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][C:11]=2[CH:12]=1.[SH:18][CH2:19][CH2:20][CH2:21][CH2:22][OH:23].Cl.CN(C)CCCN=C=NCC>ClCCl>[OH:23][CH2:22][CH2:21][CH2:20][CH2:19][S:18][C:15](=[O:17])[C@H:2]([C:3]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[C:8]([O:13][CH3:14])[CH:7]=2)[CH:12]=1)[CH3:1]

참가 물질

5

반응물 3

HCID 156391NaproxenHCID 5482614-Sulfanylbutan-1-ol2회HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

생성물 1

HCID 21075954(2S)-1-(4-Hydroxybutylthio)-2-(6-methoxy(2-naphthyl))propan-1-one수율 30%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of naproxen (5.03 g, 21.9 mmol), 4-mercapto-1-butanol (2.32 g, 21.9 mmol) and N,N-dimethylaminopyridine (DMAP) (0.534 g, 4.37 mmol) in dichloromethane (200 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDAC) (5.03 g, 26.2 mmol) as a solid, in portions. The reaction mixture was stirred for 3 hours at room temperature, then partitioned between dichloromethane and water, and the water layer was washed with more dichloromethane. The combined organic layer was washed with water and brine, then dried over magnesium sulfate. The solution was concentrated under vacuum, and the residue was purified via column chromatography, 50% ethyl acetate/hexane. The appropriate fractions were combined, and the solvent removed by rotary evaporation to give an oil, 2.647 g, which contained 19% 4-mercapto-1-butanol by weight (product weight 2.07 g, 6.5 mmol, 30% yield): 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J=2.7 Hz, 1H), 7.71 (d, J=2.3 Hz, 1H), 7.69 (d, J=1.0 Hz, 1H), 7.40 (dd, J=1.8, 8.5 Hz, 1H), 7.15 (dd, J=2.5, 8.8 Hz, 1H), 7.12 (d, J=2.3 Hz, 1H), 4.02 (q, J=7.1 Hz, 1H), 3.92 (s, 3H), 3.61-3.64 (m, 2H), 2.87 (m, 2H), 1.61 (d, J=7.1 Hz, 3H), 1.59 (m, 2H), 1.41 (m, 2H); mass spectrum (API-TIS) m/z 319 (M+H+), 336 (M+18+).

후처리

  1. custompartitioned between dichloromethane and water
  2. washthe water layer was washed with more dichloromethane
  3. washThe combined organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe solution was concentrated under vacuum
  6. customthe residue was purified via column chromatography, 50% ethyl acetate/hexane
  7. customthe solvent removed by rotary evaporation
  8. customto give an oil, 2.647 g, which

출처 및 근거

ORD 기록
ord-bab847a3feb6483491cfa7567050a96d
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304409B2

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