These common heterocyclic compound, 1073-06-9, name is 1-Bromo-3-fluorobenzene, its 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. Recommanded Product: 1-Bromo-3-fluorobenzene
Charge an oven-dried 250 mL round-bottom flask with 6-methoxy-1-tetralone (3. 0g, 17.0 mmol. ) and place under nitrogen. Dissolve the solid in toluene (30mL) and add 1-bromo-3-fluorobenzene (4. 7 mL, 42.6 mmol), sodium t-butoxide (6.5g, 68.1 mmol), palladium acetate (76mg, 0.34 mmol), and racemic BINAP (212mg, 0.34 mmol). Heat the solution to 115C and stir for 18 hours. Dilute the solution with cold 5N HC1 (50mL) and ethyl acetate (200mL). Separate the organic layer and dry over sodium sulfate, filter over a pad of celite and concentrate in vacuo. Purify the crude product using radial chromatography to give 3.4 g (74%) of the title compound. This material is used without further purification: mass spectrum (ion spray) m/z =267 (M-H). Dissolve 2- (3-fluoro-phenyl)-6-methoxy-naphthalen-l-ol (3.36g, 12.5 mmol) in N-methyl-2-pyrrolidinone (NMP) (lOmL) and add sodium hydride (500mg, 60% oil dispersion, 12.5 mmol) at room temperature. After stirring for 1 hour this solution is added to a solution of 4-fluorobenzaldehyde (2.4mL, 22.5 mmol) in NMP (lOmL) that has been heated to 185C. Continue stirring for 2.5 hours. Cool the reaction to room temperature and add pH 7 buffer (50mL) and extract with ethyl acetate (2 X 100mL). Wash the organic extracts with water and filter through a plug of silica gel. Purify the crude product using radial chromatography giving 2. 50g (54%) of the title compound and use without further purification: mass spectrum (ion spray) m/z = 371 (M-H). Charge a 100 mL round-bottom flask with 4- [2- (3-fluoro-phenyl)-6-methoxy- naphthalen-l-yloxy]-benzaldehyde (2. 5g, 6.71 mmol) and ethyl acetate (5 mL). At room temperature add 2 mL of 35% hydrogen peroxide. To this solution slowly add 2 mL of concentrated sulfuric acid. The mixture warms to approximately 40 C and returns to room temperature where it is stirred for 2 hours. Dilute the reaction with water and ethyl acetate (100 mL) and dry the organic layer over sodium sulfate, filter and concentrate in vacuo. Purify the crude product using radial chromatography eluting with CH2C12 to yield 540 mg (22%) of the title compound: mass spectrum (ion spray) m/z = 359 (M-H).
The synthetic route of 1-Bromo-3-fluorobenzene has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ELI LILLY AND COMPANY; WO2005/73204; (2005); A1;,
Bromide – Wikipedia,
bromide – Wiktionary