Water → 1,1-Dimethylethyl 4-[4-(aminocarbonyl)phenyl]-1-piperidinecarboxylate

HRID 1816333Notes

Reaction equation

HRID 1816333 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:24]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.O>ClCCl>[NH2:24][C:18]([C:17]1[CH:21]=[CH:22][C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[CH:15][CH:16]=1)=[O:19]

Participants

6

Reactant 4

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224928594-(4-Carboxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 224929041,1-Dimethylethyl 4-[4-(aminocarbonyl)phenyl]-1-piperidinecarboxylateYield 92.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[1-(tert-butoxycarbonyl)-4-piperidyl]benzoic acid (3.64 g) and 1-hydroxybenzotriazole (2.73 g) in dichloromethane (40 ml) was added 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (WSCD-HCl) (4.56 g) and the mixture was stirred at ambient temperature for 3 hours. To the reaction mixture was added water (20 ml) and an organic layer was separated and washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. A solution of the resulting residue in THF (30 ml) was added to a solution of conc. ammonium hydroxide (10 ml) in THF (30 ml) at ambient temperature and the mixture was stirred at the same temperature for 1 hour. To a reaction mixture was added ethyl acetate (200 ml) and the organic layer was separated, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The precipitate was chromatographed on silica gel (200 ml) eluting with a mixture of dichloromethane and methanol (9:1 v/v). The fractions containing the desired compound were collected and evaporated under reduced pressure to give tert-butyl 4-[4-(aminocarbonyl)phenyl]-1-piperidinecarboxylate (3.34 g).

Workup

  1. customan organic layer was separated
  2. washwashed with saturated aqueous sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. customevaporated in vacuo
  5. additionA solution of the resulting residue in THF (30 ml) was added to a solution of conc. ammonium hydroxide (10 ml) in THF (30 ml) at ambient temperature
  6. stirringthe mixture was stirred at the same temperature for 1 hour
  7. additionTo a reaction mixture was added ethyl acetate (200 ml)
  8. customthe organic layer was separated
  9. washwashed with saturated aqueous sodium chloride
  10. dry with materialdried over magnesium sulfate
  11. customevaporated in vacuo
  12. customThe precipitate was chromatographed on silica gel (200 ml)
  13. washeluting with a mixture of dichloromethane and methanol (9:1 v/v)
  14. additionThe fractions containing the desired compound
  15. customwere collected
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5f9d7052c3444283ab16968daf4a2939
Source dataset
uspto-grants-2005_04
Patent number
US06884774B2

Reaction notes

Loading…