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

HRID 1873637

Reaction equation

HRID 1873637 reaction equation
[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]

Participants

5

Reactant 3

HCID 156391NaproxenHCID 5482614-Sulfanylbutan-1-ol2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-bab847a3feb6483491cfa7567050a96d
Source dataset
uspto-grants-2012_11
Patent number
US08304409B2

Linked notes

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