2-BROMO-6-CHLOROBENZOTRIFLUORIDE

1-Bromo-3-chloro-2-(trifluoromethyl)benzene (1.0 g, 3.85 mmol), Methylboronic acid (231 mg, 3.85 mmol) andK2CO3 (1.6 g, 11.58 mmol) was dispersed in 1, 4-dioxane/water (16 mL / 4 mL).After replacing the nitrogen, Pd(dppf)Cl2 (145 mg, 0.2 mmol) was added.After replacing the nitrogen three times, the reaction was warmed to 90 C and allowed to react overnight.The reaction system was used directly for the next reaction.A flask was charged with l-bromo-3-chloro-2-(trifluorom ethyl )benzene (500 mg, 1.94 mmol, 1.00 equiv) and THF (20 mL) under nitrogen. -Butyllithium (0.93 mL, 2.32 mmol, 1.20 equiv, 2.5M in hexane) was added dropwise at -78 C. The resulting solution was stirred for 2 h at - 78 C. DMF (10 mL) was added. The resulting solution was stirred for 2 h at -78 C and quenched with water (20 mL). The mixture was extracted with EtOAc (3 x 20 mL) and the organic layers were combined, washed with brine (2 x 25 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 130 mg (32% yield) of 3-chloro-2-(trifluoromethyl)benzaldehyde as a yellow oil. LCMS (ESI, m/z): 209 [M+H]+.Example 1B; Preparation of 7-(4-{4-[3-chloro-2-(trifluoromethyl)phenyl]piperazin-1-yl}butoxy)-[1, 8]-naphthyridin-2(1H)-one; 1-(3-Chloro-2-trifluoromethyl-phenyl)-piperazine hydrochloride; To a degassed solution of toluene (200 mL) containing racemic-2, 2'-bis(diphenylphosphino)-1, 1'-binaphthyl (490 mg, 0.77 mmoles), Pd2(dba)3 (291.09 mg, 0.308 mmoles). N-Boc piperazine (28.71 g, 154.17 mmoles) and sodium tert-amylate (20.4 g, 185 mmoles) was added aryl bromide (40.0 g, 154.17 mmoles). The reaction was heated to 90 C. and stirred at that temperature for 17 hours. The reaction was cooled to approximately room temperature and washed with water (100 mL). To the organic layer was added hydrogen chloride (1.5 equiv; 231.26 mmoles; 17.52 mL; 19.27 g) and the reaction was heated to 80 C. (approximately 3 hours). The reaction was equipped with a Dean-Stark apparatus and water removed by atmospheric distillation until <0.1% water remained. The reaction was cooled to room temperature and stirred for two days. The resultant slurry was filtered, and the wet cake washed with toluene to provide 52.6 g (113% crude yield) of the product, which was sufficiently pure to use without further purification.EXAMPLE 3 3-Chloro-2-trifluoromethylbenzoic acid 1.03 g (42.4 mmol) of magnesium turnings were dissolved in THF. 2 drops of 1, 2-dibromomethane were added, and the reaction mixture was, after the exothermal reaction had set in, stirred at 32-35 C. with ice-cooling. 10.0 g (38.5 mmol) of EXAMPLE 3 3-Chloro-2-trifluoromethylbenzoic acid 1.03 g (42.4 mmol) of magnesium turnings were dissolved in THF. 2 drops of 1, 2-dibromomethane were added, and the reaction mixture was, after the exothermal reaction had set in, stirred at 32-35 C. with ice cooling. 10.0 g (38.5 mmol) of

Molecular Weight:259.45
XLogP3:4.1
Hydrogen Bond Acceptor Count:3
Exact Mass:257.90587
Monoisotopic Mass:257.90587
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes