反应详情

[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).

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