Boron trifluoride etherate → HCID 90389378, compound

Temperature

-78 °C

To a flame dried RBF was added a solution of n-butyllithium (2.5M in hexanes; 3.01 ml, 7.51 mmol) and diethyl ether (15 ml). The solution was cooled to −78° C., and 2-fluoro-6-iodotoluene (0.981 ml, 7.51 mmol) was added dropwise and the reaction was stirred at −78° C. for 10 minutes. A −78° C. premixed solution of 4-(difluoromethyl)-2-oxa-3-azabicyclo[3.1.0]hex-3-ene (1.00 g, 7.51 mmol) and boron trifluoride diethyl etherate (0.927 ml, 7.51 mmol) in toluene (10 ml) was added to the reaction via syringe. The reaction was stirred at −78° C. for 10 minutes, quenched with saturated ammonium chloride and warmed to RT. The reaction was diluted with water and EtOAc. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified via silica gel flash chromatography eluting with 0-20% ethyl acetate in hexanes to afford 4-(difluoromethyl)-4-(3-fluoro-2-methylphenyl)-2-oxa-3-azabicyclo[3.1.0]hexane (0.81 g, 3.33 mmol, 44.3% yield).

1. customTo a flame dried RBF
2. additionwas added to the reaction via syringe
3. stirringThe reaction was stirred at −78° C. for 10 minutes
4. customquenched with saturated ammonium chloride
5. temperaturewarmed to RT
6. additionThe reaction was diluted with water and EtOAc
7. customThe organic layer was separated
8. concentrationconcentrated under reduced pressure
9. customThe crude residue was purified via silica gel flash chromatography
10. washeluting with 0-20% ethyl acetate in hexanes

ORD record

ord-751ee9ac6048454598ede3d7cb0a2275

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2