HCID 86648684, compound → Tert-butyl cis(+/-)-4-amino-3-isopropoxypiperidine-1-carboxylate

HRID 1425213Notes

Reaction equation

HRID 1425213 reaction equation
C([NH:8][C@H:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C@H:10]1[O:22][CH:23]([CH3:25])[CH3:24])C1C=CC=CC=1>CO.[OH-].[Pd+2].[OH-]>[NH2:8][C@H:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][C@H:10]1[O:22][CH:23]([CH3:25])[CH3:24]

Participants

4

Reactant 1

HCID 86648684HCID 86648684, compound

Product 1

HCID 86648685Tert-butyl cis(+/-)-4-amino-3-isopropoxypiperidine-1-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

20% palladium hydroxide (wet, 60 mg) was added to a solution of tert-butyl cis(±)-4-(benzylamino)-3-isopropoxypiperidine-1-carboxylate obtained in Example (147d) (120 mg, 0.345 mmol) in methanol (1.2 mL), and the mixture was catalytically hydrogenated at room temperature for three hours. The catalyst was filtered off, and then the filtrate was concentrated under reduced pressure. A 1 N aqueous sodium hydroxide solution was added to the resulting residue, and the organic substance was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 74 mg of tert-butyl cis(±)-4-amino-3-isopropoxypiperidine-1-carboxylate as a colorless oily substance (83%). The resulting amine was dissolved in DMF (1 mL). 4-Chloro-5-ethyl-1H-imidazole-2-carboxylic acid (described in Example 1d, 54 mg, 0.29 mmol) was added, and the mixture was cooled in an ice water bath. 1-Hydroxybenzotriazole (44 mg, 0.31 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (60 mg, 0.31 mmol) were added thereto, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate, sequentially washed with brine, water and brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: chloroform/methanol) to obtain 60.6 mg of the title compound as a colorless solid (50%).

Workup

  1. filtrationThe catalyst was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionA 1 N aqueous sodium hydroxide solution was added to the resulting residue
  4. extractionthe organic substance was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-429da182408d40a0b7db363fcbab5e32
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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