Chlorotrimethylsilane → 3-(5-Nitro-pyridin-2-yl)-azetidine-1-carboxylic acid tert-butyl ester

Temperature

80 °C

Zn dust (520 mg, 7.95 mmol) was vigorously stirred in THF (2 ml) under nitrogen and 1,2 dibromoethane (84 μl, 0.97 mmol) was added. The suspension was then heated at 80° C. for 8 min and next allowed to cool to room temperature. Trimethylsilyl chloride (115 μl, 0.92 mmol) in THF (1 ml) was then added and the mixture further stirred at room temperature for 45 min. A solution of 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (1.74 g, 6.14 mmol) in THF (2 ml) was then added dropwise to the solution over a period of 15 min and the reaction mixture stirred at room temperature for 2 h. Pd2(dba)3 (90 mg, 0.10 mmol) and P(2-furyl)3 (85 mg, 0.36 mmol) were then added to the mixture, followed by 2-bromo-5-nitropyridine (1.37 g, 6.74 mmol) in THF (4 ml). The mixture was then heated at 55° C. for 3 h, cooled to room temperature and quenched with saturated aqueous NaCl. Extraction with CH2Cl2, drying (Na2SO4) of the organic phase, filtration and evaporation in vacuo provided the crude material, which was purified by flash column chromatography (heptane:ethyl acetate, 3:1) to give the title compound (1.22 g, 71%) as a light yellow oil.

1. temperatureto cool to room temperature
2. stirringthe reaction mixture stirred at room temperature for 2 h
3. temperatureThe mixture was then heated at 55° C. for 3 h
4. temperaturecooled to room temperature
5. customquenched with saturated aqueous NaCl
6. extractionExtraction with CH2Cl2
7. customdrying
8. filtration(Na2SO4) of the organic phase, filtration and evaporation in vacuo
9. customprovided the crude material, which
10. customwas purified by flash column chromatography (heptane:ethyl acetate, 3:1)

ORD record

ord-73dedf09d0d842548db11c175209cde7

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07851463B2