Citric Acid → 1-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diol

HRID 1410338Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1410338
[CH2:1]([N:8]1[C:16]2[C:11](=CC=C(C=C)C=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:20]([OH:32])(=O)[CH2:21][C:22]([CH2:27][C:28](O)=O)([C:24](O)=O)O.C[N+]1([O-])CC[O:37]CC1>CC(O)(C)C.C(O)C>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:28][CH:27]=[C:22]([CH:21]([OH:37])[CH2:20][OH:32])[CH:24]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 311Citric AcidHCID 962WaterHCID 82029Methyl morpholine oxideHCID 584862911-benzyl-6-ethenyl-1H-indazole

Produkt 1

HCID 674495831-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diolAusbeute 97,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

A sample of N1-benzyl-6-vinyl-1H-indazole (crude material, ˜24 mmol) was stirred in a mixture of tBuOH (25 mL), water (25 mL) and citric acid (10.1 g, 48.0 mmol). K2OsO4.2H2O (44 mg, 0.12 mmol, 0.5 mol %) and N-methylmorpholine-N-oxide (3.1 g, 26.4 mmol) were added, and the resulting oily, biphasic mixture stirred overnight at rt. 1H NMR of a sample showed approx. 40% conversion, and so the mixture was warmed to 50° C. (giving a single phase) for 7 h. Ethanol (50 mL) was added, and the mixture again left to stir overnight. Precipitated OsO2 was removed by filtration through celite (washing with ethanol and ethyl acetate), and the filtrate was concentrated on a rotary evaporator. The residue was taken up in 1.0 M aq. HCl and EtOAc; the layers were separated and the aqueous phase extracted with further EtOAc. The combined organic portions were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was passed through a short silica plug, eluting with EtOAc, and concentrated to afford the title compound (6.26 g, 92% over two steps) as a reddish gum. 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.38 (s, 1H), 7.27-7.18 (m, 3H), 7.16-7.09 (m, 2H), 7.04 (d, J=8.4 Hz, 1H), 5.50 (s, 2H), 4.86 (d, J=7.6 Hz, 1H), 3.78-3.68 (m, 1H), 3.60 (m, 1H), 3.46 (s, 1H), 2.84 (s, 1H). MS (ES+): 269 ([M+H]+), calcd for [C16H16N2O2+H]+ 269.1.

Aufarbeitung

  1. temperatureso the mixture was warmed to 50° C. (
  2. customgiving a single phase) for 7 h
  3. waitthe mixture again left
  4. stirringto stir overnight
  5. customPrecipitated OsO2 was removed by filtration through celite (washing with ethanol and ethyl acetate)
  6. concentrationthe filtrate was concentrated on a rotary evaporator
  7. customthe layers were separated
  8. extractionthe aqueous phase extracted with further EtOAc
  9. washThe combined organic portions were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. washeluting with EtOAc
  14. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f45cd1a5d9d741dc809380b5c3c706e6
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921545B2

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