(2S,5R)-1-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine

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

実験手順: (E)-3-(2-tert-Butoxycarbonylamino-4-chlorophenyl)-acrylic acid (595 mg, 2.0 mmol) and (2S,5R)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine (Mavunkel, Babu J. et al., WO 00/71535) (445 mg, 2.0 mmol) were dissolved in CH2Cl2, combined with EDCl.HCl (384 mg, 2.0 mmol) and stirred for 3 hours at room temperature. The reaction mixture was purified via chromatography (SiO2, EtOAc/hexanes 2/8) to yield the title compound as colorless foam (830 mg, 81%). The reaction mixture was purified via chromatography (SiO2, EtOAc/hexanes 2/8)

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

実験手順: To an ice cold solution of (trans)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine (712 mg, 3.2 mmol) and triethylamine (506 mg, 5 mmol) in CH2Cl2 (5 mL) a solution of the 5-chloro-1-benzofuran-2-carbonyl chloride (4.2 mmol) in CH2Cl2 (2 mL) was dropwise added. The reaction mixture was stirred at room temperature over night and washed with 0.5 M aqueous NaOH. The organic layer was dried, concentrated and submitted to flash column chromatography (CHCl3/MeOH; 1:0→10:1) to yield 1.05 g (82%) of the title compound. washed with 0.5 M aqueous NaOH The organic layer was dried concentrated

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

実験手順: A mixture of (trans)-1-(4-fluorobenzyl)-2,5-dimethyl-piperazine (220 mg, 1.0 mmol), 5-bromo-1-benzofuran-2-carboxylic acid (342 mg, 1.5 mmol), 1-hydroxybenzotriazol (200 mg, 1.5 mmol) and N-cyclohexylcarbodiimide, N′-methylpolystyrene (167 g, 3.0 mmol of the resin with a loading of 1.8 mmol/g) in CHCl3 was heated under 5 minutes at 110° C. in a microwave oven The mixture was allowed to attain room temperature. TBD-methyl polystyrene (1000 mg, 3 mmol of the resin with a loading of 2.9 mmol/g) was added and the mixture was agitated over night. Both resins were filtered off and washed with CHCl3 and EtOAc. The filtrate was concentrated in vacuo and the residue was submitted to flash column chromatography (toluene→toluene: EtOAc, 20:1→toluene: EtOAc, 1:1) to give the title product in 93% yield. to attain room temperature was added Both resins were filtered off washed with CHCl3 and EtOAc The filtrate was concentrated in vacuo