HCID 86648684、化合物 → Tert-butyl cis(+/-)-4-amino-3-isopropoxypiperidine-1-carboxylate

HRID 1425213ノート

反応式

HRID 1425213 の反応式
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]

参加物

4

反応物 1

HCID 86648684HCID 86648684、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 9942167Palladium hydroxide触媒HCID 887Methanol溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-429da182408d40a0b7db363fcbab5e32
出典データセット
uspto-grants-2015_01
特許番号
US08927588B2

反応ノート

読み込み中…