Nitrogen → HCID 54034338, Verbindung

HRID 2095322

Reaktionsgleichung

Reaktionsgleichung von HRID 2095322
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19](O)[CH:20]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N#N.N(C(OC(C)C)=O)=NC(OC(C)C)=O.N(C(OC(C)C)=O)NC(OC(C)C)=O>C1COCC1.C1(C)C=CC=CC=1>[Br:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([O:13][CH2:12][C@H:9]2[CH2:10][CH2:11][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:20]=1

Komponenten

9

Edukt 6

HCID 947NitrogenHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 88220Diisopropyl bicarbamateHCID 5995293-Bromo-5-hydroxypyridineHCID 11074142(R)-1-Boc-2-azetidinemethanol

Produkt 1

HCID 54034338HCID 54034338, VerbindungAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

[1-(tert-Butoxycarbonyl)-2(R)-azetidinyl]methanol (1.42 g, 7.60 mmol) was dried by azeotropic evaporation with toluene (3×10 mL) in a 50 mL round-bottom flask. 3-Bromo-5-hydroxypyridine (1.32 g, 7.60 mmol) and triphenylphosphine (2.20 g, 8.40 mmol, 1.1 equiv.) were added. The flask was capped with a rubber septum, and the atmosphere was exchanged three times with N2 (balloon). Anhydrous THF (25 mL) was added via syringe, and the mixture was stirred in an ice bath until all reagents were dissolved. Diisopropyl azodicarboxylate (DIAD, 1.76 mL, 8.40 mmol, 1.1 equiv.) was added dropwise in several portions over 30 min. The resulting mixture was stirred in the thawing ice bath overnight. After removal of the THF, the residue was purified by CC on SiO2 (25×3.8 cm, EtOAc/hexanes 1:4 to 3:7) to give crude product. A 1H NMR spectrum showed that the material was a mixture with diisopropyl hydrazodicarboxylate (containing approx. 56% of the title compound by mass), which was used directly for the next step. 1H NMR (CDCl3, 400 MHz; signals of the title compound only) δ 8.29 (d, 1H, J=1.8 Hz), 8.28 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=2.3 Hz), 4.55-4.47 (m, 1H), 4.33 (br s, 1H), 4.13-4.09 (m, 1H), 3.93-3.85 (m, 2H), 2.40-2.20 (m, 2H), 1.43 (s, 9H).

Aufarbeitung

  1. customThe flask was capped with a rubber septum
  2. dissolutionwere dissolved
  3. stirringThe resulting mixture was stirred in the thawing ice bath overnight
  4. customAfter removal of the THF
  5. customthe residue was purified by CC on SiO2 (25×3.8 cm, EtOAc/hexanes 1:4 to 3:7)
  6. customto give crude product

Quellen und Nachweise

ORD-Eintrag
ord-828a8ba7c01044be92aec86547898904
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08445684B2

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