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

HRID 1425213노트

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HRID 1425213 반응식
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]

참가 물질

4

반응물 1

HCID 86648684HCID 86648684, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매HCID 887Methanol용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-429da182408d40a0b7db363fcbab5e32
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927588B2

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