反应详情

To a stirred mixture of 4-hydroxy-N,N,2-trimethyl-1-[(4-methylphenyl)sulfonyl]-1H-benzimidazole-6-carboxamide (21.2 g, 56.8 mmol, STEP 4), (+)-5,7-difluoro-3,4-dihydro-2H-chromen-4-ol (15.86 g, 85.1 mmol, STEP 8) and tributylphosphine (22.9 g, 113 mmol) in toluene (840 mL) was added 1,1′-(azodicarbonyl)dipiperidine (ADDP) (19.3 g, 76.5 mmol) at room temperature. After stirring at room temperature for 2 hours, the reaction mixture was filtered through a pad of Celite and washed with ethyl acetate (300 mL). The filtrate was concentrated in vacuum. The residue was purified by column chromatography on silica get (ethyl acetate:hexane gradient elution from 1:20 to 20:1) to afford crude solids (27.0 g). The solids were recrystallized from 2-propanol (130 mL) to give the title compound as a colorless crystal (23.2 g, 75%, >99% ee)

1. filtrationthe reaction mixture was filtered through a pad of Celite
2. washwashed with ethyl acetate (300 mL)
3. concentrationThe filtrate was concentrated in vacuum
4. customThe residue was purified by column chromatography on silica
5. customget
6. wash(ethyl acetate:hexane gradient elution from 1:20 to 20:1)
7. customto afford crude solids (27.0 g)
8. customThe solids were recrystallized from 2-propanol (130 mL)