反应详情

A mixture of intermediate (12) (0.095 mol) in a mixture of HCl in 2-propanol (100 ml) and HCl (500 ml) was stirred and refluxed for one hour. The reaction mixture was cooled. The solvent was evaporated. The residue was taken up into DCM and washed with NH3/H2O. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/(CH3OH/NH3) 90/10). The product fractions were collected and the solvent was evaporated. A sample (2 g) of this fraction was crystallized from DIPE with a small amount of ACN, filtered off, washed and dried, yielding 1.8 g of (3S-trans)-8-chloro-3,4-dihydro-N-[(3-hydroxy-4-piperidinyl)methyl]-2H-1,5-benzodioxepin-6-carboxamide (intermediate 3-t) (mp: 114° C.) [α]D20=−14.34° (c=24.41 mg/5 ml in CH3OH).

1. temperaturerefluxed for one hour
2. temperatureThe reaction mixture was cooled
3. customThe solvent was evaporated
4. washwashed with NH3/H2O
5. customThe organic layer was separated
6. customdried
7. filtrationfiltered
8. customthe solvent was evaporated
9. customThe residue was purified over silica gel on a glass
10. filtrationfilter (eluent: CH2Cl2/(CH3OH/NH3) 90/10)
11. customThe product fractions were collected
12. customthe solvent was evaporated
13. customA sample (2 g) of this fraction was crystallized from DIPE with a small amount of ACN
14. filtrationfiltered off
15. washwashed
16. customdried