Carbon Dioxide → 2-Fluoroadenosine

HRID 566695Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 566695
[FH:1].[CH:2]1[N:6]([CH:7]2[O:11][CH:10]([CH2:12][OH:13])[CH:9]([OH:14])[CH:8]2[OH:15])[C:5]2[N:16]=[C:17](N)[N:18]=[C:19]([NH2:20])[C:4]=2[N:3]=1.C(ON=O)(C)(C)C.C(=O)(O)[O-].[Na+].C(=O)=O>N1C=CC=CC=1.O.C(OCC)(=O)C.C(OCC)(=O)C.CO>[F:1][C:17]1[N:18]=[C:19]([NH2:20])[C:4]2[N:3]=[CH:2][N:6]([C:5]=2[N:16]=1)[C@@H:7]1[O:11][C@H:10]([CH2:12][OH:13])[C@@H:9]([OH:14])[C@H:8]1[OH:15]

Komponenten

11

Edukt 6

HCID 280Carbon DioxideHCID 10906Tert-Butyl nitriteHCID 14917Hydrofluoric AcidHCID 2220762-(2,6-Diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diolHCID 516892Sodium BicarbonateHCID 178435160HCID 178435160, Verbindung

Produkt 1

HCID 89752-Fluoroadenosine

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 21584119Ethylacetate methanolLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

A 2 L polyethylene bottle was equipped with a magnetic stirrer, thermometer, dry ice/acetone bath and a stream of argon gas. Anhydrous pyridine (750 mL) was added and the solution was cooled to −20° C. To this was added 70% hydrogen fluoride in pyridine (500 mL). 2,6-diaminopurine riboside (1,2-aminoadenosine, 105 g, 0.372 mol, R.I. Chemical, Orange, Calif., Reliable Biopharmaceuticals, St. Louis, Mo.) was suspended in the liquid. Tert-butylnitrite (90 mL, 0.76 mol) was added in one portion and the reaction was stirred at 9-11° C. until the reaction was complete as judged by TLC (3 h, Rf 0.20, starting material; Rf 0.40, product, ethyl acetate-methanol 4:1). Sodium bicarbonate (3 kg) was suspended with manual stirring in water (2 L) in a 20 L bucket. The reaction solution was slowly poured (to allow for evolution of carbon dioxide) into the aqueous layer with vigorous stirring. Ethyl acetate was added periodically in small portions to reduce foaming. The resulting suspension was extracted with ethyl acetate (5×1 L). The organic layers were combined and concentrated to a solid. The solid was mostly dissolved in warm methanol (300 mL). The solution was cooled in a ice water bath and the resulting solid was collected, rinsed with methanol (2×100 mL) and dried under vacuum (1 mm Hg, 25° C., 24 h) to give 76 g of product as a gold solid, mp 214-215° C. The mother liquor was concentrated to a solid and recrystallized from water (600 mL) to give in three crops an additional 18.3 g of similar quality product for a total of 90.3 g (85%). H-NMR (DMSO-d6) δ 3.4-3.8 (m, 2, 5′ and 5″-H), 3.95 (m, 1, 4′-H), 4.14 (m, 1, 3′-H), 4.53 (m, 1, 2′-H), 5.04 (t, 1, 5′-OH), 5.23 (d, 1, 3′-OH), 5.50 (d, 1, 2′-OH), 5.80 (d, 1, 1′-H), 7.89 (br s, 2, NH2), 8.37 (s, 1, 8-H).

Aufarbeitung

  1. extractionThe resulting suspension was extracted with ethyl acetate (5×1 L)
  2. concentrationconcentrated to a solid
  3. dissolutionThe solid was mostly dissolved in warm methanol (300 mL)
  4. temperatureThe solution was cooled in a ice water bath
  5. customthe resulting solid was collected
  6. washrinsed with methanol (2×100 mL)
  7. customdried under vacuum (1 mm Hg, 25° C., 24 h)

Quellen und Nachweise

ORD-Eintrag
ord-b3d4bba2923f4028900321a28899ea81
Quelldatensatz
uspto-grants-2001_01
Patentnummer
US06175004B1

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