反应详情

温度

40 °C

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 36% 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 5% 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: 80.9%, purity: 99% (HPLC)].

1. additionTo the reaction mixture were added
2. extraction36% hydrochloric acid (340.5 g), water (1,260 ml) and toluene (1,260 ml), and extraction
3. washThe organic layer was washed with a 5% aqueous sodium hydrogencarbonate solution (1,260 ml)
4. distillationsubjected to vacuum distillation
5. customto distil off the solvent
6. additionTo the residue were added 2-propanol (378 ml) and methanol (756 ml)
7. dissolutionthe residue was dissolved
8. temperaturewith heating
9. additionTo the solution was added, as a seed crystal, 2.7 g of the 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene
10. customproduced by the method of Reference Example 2, at 39.7° C.
11. stirringby stirring at 0.7 to 5.0° C. for 13 hours
12. filtrationThe separated-out crystals were collected by filtration
13. washwashed with methanol (251 ml)
14. customvacuum-dried