3-[(4-bromo-2-fluorophenyl)methylamino]butan-1-ol

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-(4-bromo-2-fluorobenzylamino)butan-1-ol (800 mg, 2.9 mmol) and Burgess' Reagent (2.07 g, 8.7 mmol) in anhydrous THF (10 mL) was heated at 65° C. for 2 hours. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel chromatography using petroleumn ether/EtOAc (6/1) as eluting solvents to afford methyl 6-[(4-bromo-2-fluorophenyl)methyl]-5-methyl-1,1-dioxo-1λ6,2,6-thiadi-azinane-2-carboxylate as light yellow oil. (900 mg, 79%). 1H NMR (500 MHz, CDCl3) δ 7.45 (t, 1H), 7.17 (d, 1H), 7.25-7.23 (m, 1H), 4.44 (dd, 2H), 4.20-4.25 (m, 1H), 3.92-3.99 (m, 1H), 3.88 (s, 3H), 3.45-3.51 (m, 1H), 1.87-2.00 (m, 2H), 1.23 (d, 3H); LCMS (ESI): m/z=397.0 [M+H]+. The reaction mixture was concentrated under reduced pressure The crude product was purified by silica gel chromatography as eluting solvents

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-aminobutan-1-ol (1.8 g, 20.2 mmol), 4-bromo-2-fluorobenzaldehyde (4.1 g, 20.2 mmol), and ZnCl2 (28 mg, 0.202 mmol) in MeOH (20 mL) was stirred at ambient temperature for 1 hour. To the mixture at 0° C. was added NaBH4 (3.84 g, 101 mmol) and stirred at ambient temperature for 22 hours. The reaction mixture was quenched with H2O and extracted with EtOAc (30 mL×4). The extracts were combined, washed with brine (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using petroleumn ether/EtOAc (5/1) and EtOAc/NEt3 (500/1) as eluting solvents to afford 3-(4-bromo-2-fluorobenzylamino)butan-1-ol as corlorless oil (3.2 g, 57%). 1H-NMR (500 MHz, CDCl3) δ 7.25-7.20 (m, 3H), 3.90 (d, 1H), 3.87-3.83 (m, 1H), 3.77-3.173 (m, 2H), 3.00-2.93 (m, 2H), 1.77-1.71 (m, 1H), 1.59-1.52 (m, 1H), 1.20 (d, 3H); LCMS (ESI): m/z=276.1 [M+H]+. stirred at ambient temperature for 22 hours The reaction mixture was quenched with H2O extracted with EtOAc (30 mL×4) washed with brine (20 mL) dried over sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel chromatography as eluting solvents