2-(5-bromo-2-fluorobenzyl)benzo[b]thiophene

Will 35.4g (105mmol)Benzo[b]thiophene-2-methanol, α-(5-bromo-2-fluorophenyl) (compound of formula 3) is solubleIn 800 mL of dichloromethane, And cooled to -20 ° C, To this solution was added 36.5 mL (230 mmol)Triethylsilane and 15.2 mL (120 mmol) of boron trifluoride etherate, The mixture was stirred at -20 ° C for 30 minutes.A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture.The organic phase was separated and dried over magnesium sulfate.It is then filtered and dried under vacuum.The obtained crude product was purified by column chromatography (ethyl acetate-hexane).Obtaining benzo[b]thiophene, 2-[(5-Bromo-2-fluorophenyl)methyl](Compound 4) 30.4g;purity99.5percent; yield 90.1percent;General procedure: To a cold (-78 °C) solution of 50 (16.6 g, 124 mmol) in THF (200 mL) was added n-BuLi (1.60 M in hexane; 78.5 mL, 124 mmol) and the mixture was stirred at -78 °C for 1.5 h. To the reaction mixture was added a solution of 64 (29.0 g, 118 mmol) in THF (300 mL) and the mixture was stirred at -78 °C for 2 h. To the reaction mixture was added HUnder nitrogen protection, in a four-necked flask equipped with a mechanical stirring and a thermometer, 20.1 g of benzothiophene and 180 mL of 2-methyltetrahydrofuran were stirred and dissolved, and the temperature was lowered to -40--35 ° C, and 90 ml of butyllithium was added thereto. 3 hours after the reaction at the temperature, 40.3 g of 2-fluoro-5-bromobenzaldehyde was added. After the reaction was completed at this temperature for 10 hours, the temperature was raised to room temperature, and the pH was adjusted to 7 by adding hydrochloric acid. 2. Under a nitrogen atmosphere, Compound 2 and n-hexane were added to a four-necked flask equipped with a mechanical stirring and a thermometer, and the mixture was stirred and dissolved. Then, trifluoroacetic acid and triphenylsilane (5 eq) were added, and then reacted at -10 ° C for 1 hour. After the completion of the monitoring reaction, the temperature was raised to room temperature, and the target compound was obtained as a white solid, 41 g.The yield in two steps was 81percent.Third step: Synthesis of 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene; Acetonitrile (1, 260 ml)was added to 2-[(5-bromo-2-fluorophenyl)(chloro)methyl]-1-benzothiophene (265.69 g) and the mixture was heated to 40°C. The resulting solution was added to a water (1, 260 ml) solution of sodium borohydride (113.0 g) and sodium hydroxide (14.9 g) at 59.0 to 67.9°C, followed by stirring at 24.1 to 67.5°C for 17.5 hours. To the reaction mixture were added 36percent hydrochloric acid (340.5 g), water (1, 260 ml) and toluene (1, 260 ml), and extraction was conducted. The organic layer was washed with a 5percent aqueous sodium hydrogencarbonate solution (1, 260 ml) and subjected to vacuum distillation to distil off the solvent. To the residue were added 2-propanol (378 ml) and methanol (756 ml), and the residue was dissolved with heating. To the solution was added, as a seed crystal, 2.7 g of the 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene produced by the method of Reference Example 2, at 39.7°C, followed by stirring at 0.7 to 5.0°C for 13 hours. The separated-out crystals were collected by filtration, washed with methanol (251 ml), and vacuum-dried to obtain, as white crystals, 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene [194.05 g, yield: 80.9percent, purity: 99percent (HPLC)].

Molecular Weight:321.2
XLogP3:5.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:319.96706
Monoisotopic Mass:319.96706
Topological Polar Surface Area:28.2
Heavy Atom Count:18
Complexity:286
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes