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

HRID 1264654Notes

Reaction equation

HRID 1264654 reaction equation
O.[Cl:2][C:3]1[CH:4]=[C:5]([C:14]([NH:16][CH2:17][C@@H:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][C@H:19]2[OH:31])=[O:15])[C:6]2[O:12][CH2:11][CH2:10][CH2:9][O:8][C:7]=2[CH:13]=1>Cl.CC(O)C>[Cl:2][C:3]1[CH:4]=[C:5]([C:14]([NH:16][CH2:17][C@@H:18]2[CH2:23][CH2:22][NH:21][CH2:20][C@H:19]2[OH:31])=[O:15])[C:6]2[O:12][CH2:11][CH2:10][CH2:9][O:8][C:7]=2[CH:13]=1

Participants

4

Reactant 1

HCID 205757661,1-Dimethylethyl(3s-trans)-4-[[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate

Product 1

HCID 11279261(3s-trans)-8-Chloro-3,4-dihydro-n-[(3-hydroxy4-piperidinyl)methyl]-2h-1,5-benzodioxepin-6-carboxamideYield 5.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 3776IsopropanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-afbddde147e2469789c9ddf84cbd7566
Source dataset
uspto-grants-2003_04
Patent number
US06544997B1

Reaction notes

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