Application of 1435-51-4,Some common heterocyclic compound, 1435-51-4, name is 1,3-Dibromo-5-fluorobenzene, molecular formula is C6H3Br2F, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Preparation 4.; (4- (3-bromo-5-fluoro-phenyl)-cyclohex-3-enyl)-dimethyl-amine (enantiomer 2); Dissolve 1, 3-dibromo-5-fluoro-benzene (19.8 g, 77.90 mmol) in dry diethyl ether (300 mL) and cool to-60C. Add 1.6M n-BuLi in hexanes (50.9 mL, 81.44 mmol) dropwise over 15 min. and stir an additional 15 min. Add a pre-cooled (-60C) solution of 4-dimethylamino-cyclohexanone (10.0 g, 70.8 mmol) in diethyl ether (200 mL) dropwise over 30 min. Stir at-60C to-20C for 2 hr. , then warm to ambient temperature and stir for 1 hr. Quench the reaction with water (200 mL) and extract with ethyl acetate (3 x 200 mL). Dry over sodium sulfate, filter and concentrate. Purify the residue by flash chromatography (15% 2M NH3/MeOH in DCM) to obtain 1- (3-Bromo-5- fluoro-phenyl) -4-dimethylamino-cyclohexanol as a white foam (14. 5 g, 64.8%). MS (ES) m/z = 316 (M-H)-, 318 (M+H) +, 1H NMR (CDC13) : 8 7.41 (d, 1H, J= 2 Hz), 7.15 (m, 2H), 2.3 (m, 8H), 1.78 (m, 8H). Combine 1- (3-bromo-5-fluoro-phenyl)-4-dimethylamino-cyclohexanol (14.5 g, 45.9 mmol), p-TsOH (21.8 g, 114.6 mmol) and toluene (200 mL) and heat to reflux for 3 hr. Cool to ambient temperature and partition between ethyl acetate (500 mL) and 1M NaOH solution (250 mL). Wash the organic layer with 1M NaOH solution (200 mL) and saturated aqueous NaCl (200 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by chromatography (silica gel, 10% 2M NH3/MeOH in DCM) to obtain (4- (3- bromo-5-fluoro-phenyl) -cyclohex-3-enyl) -dimethyl-amine (10.8 g, 79%): MS (ES) m/z= 298 (M-H)’, 300 (M+H) ; 1H NMR (CDC13) : 8 7.25 (d, 1H, J= 2 Hz), 7.02 (dd, 1H, J= 8 Hz, J= 2 Hz), 6.9 (dd, 1H, J= 8 Hz, J= 2 Hz), 6.04 (m, 1H), 2. 38 (m, 4H), 2.27 (s, 6H), 2.09 (m, 2H), 1.48 (m, 1H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,3-Dibromo-5-fluorobenzene, its application will become more common.
Reference:
Patent; ELI LILLY AND COMPANY; WO2005/61439; (2005); A1;,
Bromide – Wikipedia,
bromide – Wiktionary