2-Methyl-2-nitro-1,3-propanediol → 3-Hydroxy-2-methyl-2-nitropropyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

HRID 1873621Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1873621
C1(N=C=NC2CCCCC2)CCCCC1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[C:23]([C@H:28]([CH3:32])[C:29]([OH:31])=[O:30])[CH:22]=[CH:21]2.[N+:33]([C:36]([CH3:41])([CH2:39]O)[CH2:37][OH:38])([O-:35])=[O:34]>C(Cl)Cl.C1COCC1>[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[C:23]([C@H:28]([CH3:32])[C:29]([O:31][CH2:39][C:36]([CH3:41])([N+:33]([O-:35])=[O:34])[CH2:37][OH:38])=[O:30])[CH:22]=[CH:21]2

Komponenten

6

Edukt 3

HCID 64802-Methyl-2-nitro-1,3-propanediolHCID 10868DicyclohexylcarbodiimideHCID 156391Naproxen

Produkt 1

HCID 210759633-Hydroxy-2-methyl-2-nitropropyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 1,3-dicyclohexylcarbodiimide (4.23 g, 20.5 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.34 g, 18.9 mmol), and 2-nitro-2-methyl-1,3-propanediol (2.56 g, 19.0 mmol) in CH2Cl2 (50 mL) and THF (50 mL) was stirred at ambient temperature overnight. The solvent was evaporated and EtOAc (100 mL) was added to the resulting crude material, cooled in a dry-ice bath and the byproduct, dicyclohexyl urea was removed by filtration. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (1:3, Rf=0.1) to give the title compound (a mixture of diasteromers) as an oil (2.77 g, 42% yield). 1H NMR (300 MHz, CDCl3) δ 7.69-7.60 (m, 3H), 7.34-7.3 (m, 1H), 7.14-7.08 (m, 2H), 4.44 (d, J=4.2 Hz, 2H), 3.86 (s, 3H), 3.85 (q, J=7.2 Hz, 1H), 3.7 (m, 1H), 1.55 (d, J=7.2 Hz, 3H), 1.36 & 1.40 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 174.14, 174.02, 157.57, 134.53, 134.51, 133.64, 129.13, 128.7, 127.17, 125.87, 125.84, 119.0, 105.47, 89.53, 89.42, 64.67, 64.52, 64.19, 55.12, 45.04, 18.25, 18.03, 17.82, 17.79. Mass spectrum (API-TIS) m/z 348 (MH)+.

Aufarbeitung

  1. customThe solvent was evaporated
  2. additionEtOAc (100 mL) was added to the resulting crude material
  3. temperaturecooled in a dry-ice bath
  4. customthe byproduct, dicyclohexyl urea was removed by filtration
  5. customThe product was separated by silica gel column chromatography
  6. washeluting with ethyl acetate/hexane (1:3, Rf=0.1)

Quellen und Nachweise

ORD-Eintrag
ord-3d2aa3f47b314fa3b622cf16ed07bc69
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08304409B2

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