Dichloromethane → 1,1-Dimethylethyl(3s-trans)-4-[[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate

Intermediate (11) (0.1 mol), triethylamine (0.1 mol) and DCM (500 ml) were stirred at a temperature below 10° C. Ethyl chloroformate (0.1 mol) was added dropwise at temperature below 10° C. The mixture was stirred for 30 minutes at a temperature below 10° C. A solution of 1,1-dimethylethyl (3S-trans)-4-(aminomethyl)-3-hydroxy-1-piperidinecarboxylate (0.1 mol) in triethylamine (250 ml) was added at a temperature below 10° C. The reaction mixture was stirred for one hour at room temperature. The mixture was concentrated to half the initial volume. The concentrate was washed with water, with H2O/50% NaOH, and again with water. The organic layer was separated, dried, filtered and the solvent was evaporated, yielding 44 g of 1,1-dimethylethyl(3S-trans)-4-[[[(8-chloro-3,4-dihydro-2H-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate (intermediate 12) (mp: 88° C.; sticky) [α]D20=−0.97° (c=25.71 mg/5 ml in CH3OH).

1. stirringThe reaction mixture was stirred for one hour at room temperature
2. concentrationThe mixture was concentrated to half the initial volume
3. washThe concentrate was washed with water, with H2O/50% NaOH
4. customThe organic layer was separated
5. customdried
6. filtrationfiltered
7. customthe solvent was evaporated

ORD record

ord-a79f497e52ec48edb574640fc97bad90

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06544997B1