C([Li])CCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9](I)[C:8]=1[CH3:14].[F:15][CH:16]([F:23])[C:17]1[CH:22]2[CH:20]([CH2:21]2)[O:19][N:18]=1.B(F)(F)F.CCOCC>C1(C)C=CC=CC=1.C(OCC)C>[F:15][CH:16]([F:23])[C:17]1([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([F:6])[C:8]=2[CH3:14])[CH:22]2[CH:20]([CH2:21]2)[O:19][NH:18]1To 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).
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