tert-Butyl 4-bromo-2-fluorobenzoate

Step 1 : Preparation of tert-butyl 4-bromo-2-fluoro-benzoate To a solution of 4-bromo-2-fluoro-benzoic acid (100.0 g, 0.46 mol) in THF/t-BuOH (800 mL/400 mL) was added BocStep 1. 4-Bromo-2-fluorobenzoic acid (1 ) (10 g, 46 mmol) was suspended in DCM (100 mL), treated with oxalyl chloride (12.0 mL, 137 mmol) followed by DMF (36 μ, 0.46 mmol) and the mixture was stirred at RT for 5 h. The mixture was concentrated in vacuo to give a yellow oil which was redissolved in THF and added dropwise to a mixture of pyridine (5.5 mL, 68 mmol) and 'BuOH (8.7 mL, 91 mmol) in THF (100 mL) at 0°C. The mixture was then warmed to RT, stirred at RT for 18 h, then at 50°C for 5 h. The mixture was cooled to RT, concentrated in vacuo and the residue was purified by silica gel chromatography (220 g, 0-10percent EtOAc in isohexane) to afford the title compound (2) (0862) (9.3 g, 74percent) as a colourless oil: To a 50 mL round-bottom flask purged and maintained under an inert atmosphere of nitrogen was added (1S, 4S, 5R)-5-[[4-cyclopropyl-l-(2, 6-dichlorophenyl)-1H-l, 2, 3-triazol-5- yl]methoxy]-2-azabicyclo[2.2.1]heptane 52i (120 mg, 0.32 mmol, 1.00 equiv.), toluene (3 mL), Pd(OAc)2 (14 mg, 0.06 mmol, 0.20 equiv.), Xantphos (36 mg, 0.06 mmol, 0.20 equiv.), Cs2CO3 (310 mg, 0.95 mmol, 3.00 equiv.), and To a 250 mL round-bottom flask was added (1S, 4S, 5R)-5-[[4-cyclopropyl-l-(2, 6- dichlorophenyl)-1H-l, 2, 3-triazol-5-yl]methoxy]-2-azabicyclo[2.2.1]heptane 52i (40 mg, 0.11 mmol, 1.00 equiv.), tert-butyl 4-bromobenzoate (40 mg, 0.16 mmol, 1.50 equiv.), Pd2(dba)3 (20 mg, 0.02 mmol, 0.20 equiv.), BINAP (26 mg, 0.04 mmol, 0.40 equiv.), Cs2CO3 (138 mg, 0.42 mmol, 4.00 equiv.), and toluene (5 mL). The resulting mixture was heated at 110°C overnight. After cooling to room temperature, the mixture was diluted with H2O (50 mL), and extracted with ethyl acetate (100 mL x 2). The combined organic extracts were washed with brine (100 mL x 2), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography eluting with ethyl acetate/hexane (1 :2) to afford tert-butyl 4- [(1S, 4S, 5R)-5-[[4-cyclopropyl-l-(2, 6-dichlorophenyl)-1H-l, 2, 3-triazol-5-yl]methoxy]-2- azabicyclo[2.2.1]heptan-2-yl]benzoate 52j (50 mg, 85percent) as a yellow oil.To a 50 mL round-bottom flask was added Cs2CO3 (480 mg, 1.47 mmol, 3.00 equiv.), toluene (4 mL), To an 8 mL sealed tube was added

Molecular Weight:275.11
XLogP3:3.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:274.00047
Monoisotopic Mass:274.00047
Topological Polar Surface Area:26.3
Heavy Atom Count:15
Complexity:237
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes