Tris(hydroxymethyl)nitromethane → 3-Hydroxy-2-(hydroxymethyl)-2-nitropropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate

HRID 1514766

Reaktionsgleichung

Reaktionsgleichung von HRID 1514766
[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.[OH:18][CH2:19][C:20]([N+:25]([O-:27])=[O:26])([CH2:23]O)[CH2:21][OH:22].Cl.CN(C)CCCN=C=NCC.N(C(C)C)(C(C)C)CC>CC(C)=O>[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][C:20]([CH2:21][OH:22])([N+:25]([O-:27])=[O:26])[CH2:19][OH:18])=[O:15])[CH:7]=[CH:6]2

Komponenten

6

Edukt 4

HCID 31337Tris(hydroxymethyl)nitromethaneHCID 81531DiisopropylethylamineHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Produkt 1

HCID 210759623-Hydroxy-2-(hydroxymethyl)-2-nitropropyl (2S)-2-(6-methoxy(2-naphthyl))propanoateAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 180AcetoneLösungsmittel

Versuchsvorschrift

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.27 g, 18.5 mmol), 2-hydroxymethyl-2-nitro-1,3-propanediol (2.89 g, 19.1 mmol), N,N-dimethylaminopyridine (DMAP, 0.88 g, 7.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.86 g, 25.4 mmol) and NEt(i-Pr)2 (11 mL, 63.2 mmol) in acetone (100 mL) was stirred at ambient temperature overnight. The reaction mixture was evaporated to dryness and the residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2). The combined organic layer was back washed with water and brine, dried over Na2SO4, filtered, concentrated and dried under vacuum. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2) to give the title compound as a white solid (2.48 g, 39% yield). Mp 124-126° C. 1H NMR (300 MHz, 10% CD3OD/CDCl3) δ 7.73-7.64 (m, 3H), 7.37-7.33 (m, 1H), 7.17-7.12 (m, 2H), 4.44 (d, J=2.6 Hz, 2H), 3.92 (s, 3H), 3.9-3.7 (m, 5H), 3.4 (br, 2H), 1.58 (d, J=7.2 Hz, 3H). 13C NMR (75 MHz, 10% CD3OD/CDCl3) δ 174.1, 157.4, 134.5, 133.5, 129.0, 128.6, 127.0, 125.7, 118.8, 105.4, 92.4, 61.2, 60.1, 55.0, 45.0, 17.7.

Aufarbeitung

  1. customThe reaction mixture was evaporated to dryness
  2. customthe residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
  3. washThe combined organic layer was back washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customdried under vacuum
  8. customThe product was separated by silica gel column chromatography
  9. washeluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

Quellen und Nachweise

ORD-Eintrag
ord-4fb6aef57b30467798db837750e4cede
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222277B2

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