Hydrochloric Acid → tert-butyl 4-{[(2R)-2-(benzyloxy)propanoyl]amino}piperidine-1-carboxylate

HRID 1026541Notes

Reaction equation

HRID 1026541 reaction equation
[CH2:1]([O:8][C@H:9]([CH3:13])[C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.Cl>ClCCl>[CH2:1]([O:8][C@H:9]([CH3:13])[C:10]([NH:14][CH:15]1[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7000104(2R)-2-phenylmethoxypropanoic acid

Product 1

HCID 52331793tert-butyl 4-{[(2R)-2-(benzyloxy)propanoyl]amino}piperidine-1-carboxylateYield 96.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a dichloromethane solution (1000 ml) of (2R)-2-(benzyloxy)propionic acid (51.7 g) and tert-butyl 4-aminopiperidine-1-carboxylate (63.2 g) were added at room temperature 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60.5 g) and 1-hydroxybenzotriazole monohydrate (42.7 g), followed by stirring overnight. The reaction solution was poured into a 0.5 N aqueous hydrochloric acid solution, and extracted with dichloromethane. The organic layer was washed sequentially with water, a saturated aqueous sodium hydrogen carbonate solution, water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford tert-butyl 4-{[(2R)-2-(benzyloxy)propanoyl]amino}piperidine-1-carboxylate (100 g).

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic layer was washed sequentially with water
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution, water and saturated sodium chloride solution, dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6f93400e3e4f4c49a26fafeab9214aec
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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