2-BroMo-3-(trifluoroMethoxy)pyridine

2-Bromo-3-trifluoromethoxypyridine (23); A solution of 2-chloro-3-trifluoromethoxypyridine (8, 4.0 g, 20.2 mmol) and bromotrimethylsilane (6.3 g, 5.4 mL, 40.4 mmol, 2 eq) in propionitrile (20 mL) was heated under reflux for 24 h. GC monitoring indicated 100percent conversion. The mixture was distilled in vacuum to afford pure 2-bromo-3-trifluoromethoxypyridine (23, 3.9 g, 16.1 mmol, 80percent) as a colorless oil; b.p. 63-67 2-Bromo-3-trifluoromethoxypyridine (23); A solution of 2-chloro-3-trifluoromethoxypyridine (8, 4.0 g, 20.2 mmol) and bromotrimethylsilane (6.3 g, 5.4 mL, 40.4 mmol, 2 eq) in propionitrile (20 mL) was heated under reflux for 24 h. GC monitoring indicated 100percent conversion. The mixture was distilled in vacuum to afford pure 2-bromo-3-trifluoromethoxypyridine (23, 3.9 g, 16.1 mmol, 80percent) as a colorless oil; b.p. 63-67 To a stirred mixture of 2-bromo-3- (trifluoromethoxy) pyridine (300 mg, 1.24 mmol, 1 equiv) and Zn (CN) 2 (291.2 mg, 2.48 mmol, 2 equiv) in THF (15 mL) and H 2O (3 mL) , t-BuXantPhos-Pd-G3 (197.0 mg, 0.25 mmol, 0.2 equiv) and t-BuXantPhos (171.3 mg, 0.25 mmol, 0.2 equiv) under nitrogen atmosphere at RT. The resulted mixture was stirred for 2h at 80 under nitrogen atmosphere. The solvent was removed under reduced pressure. The residue was purified by Prep-TLC (CH 2Cl 2 /MeOH 20: 1) to afford 3- (trifluoromethoxy) pyridine-2-carbonitrile (200 mg, 85.76%) as a white solid. LCMS: m/z (ESI) , [M+H] + = 188.9.A microwave vial was charged with (iS, 25)-l-A-(6-fluoro-l, 3-beiizothiazol-2- yl)cyclopentane-l, 2-di amine hydrochloride (Intermediate 1; 172 mg, 0.60 mmol), molybdenum hexacarbonyl (79 mg, 0.30 mmol), tri-tert-butylphosphonium (0587) tetrafiuoroborate (5 mg, 0.018 mmol), 2-Bromo-3-trifluoromethoxypyridine (23); A solution of 2-chloro-3-trifluoromethoxypyridine (8, 4.0 g, 20.2 mmol) and bromotrimethylsilane (6.3 g, 5.4 mL, 40.4 mmol, 2 eq) in propionitrile (20 mL) was heated under reflux for 24 h. GC monitoring indicated 100% conversion. The mixture was distilled in vacuum to afford pure 2-Bromo-3-trifluoromethoxypyridine (23); A solution of 2-chloro-3-trifluoromethoxypyridine (8, 4.0 g, 20.2 mmol) and bromotrimethylsilane (6.3 g, 5.4 mL, 40.4 mmol, 2 eq) in propionitrile (20 mL) was heated under reflux for 24 h. GC monitoring indicated 100% conversion. The mixture was distilled in vacuum to afford pure

Molecular Weight:241.99
XLogP3:2.6
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:240.93501
Monoisotopic Mass:240.93501
Topological Polar Surface Area:22.1
Heavy Atom Count:12
Complexity:152
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes