1,1-Dimethylethyl(3s-trans)-4-[[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate → (3s-trans)-8-Chloro-3,4-dihydro-n-[(3-hydroxy4-piperidinyl)methyl]-2h-1,5-benzodioxepin-6-carboxamide

Participants

Reaction Steps

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-hydroxy4-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).

Provenance & Evidence