Ethyl Acetate → (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1972089ノート

反応式

HRID 1972089 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH:12]2[CH:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:15]=[N+:16]=[N-:17].[Na+].CCOC(C)=O>CN(C=O)C.CC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]([N:15]=[N+:16]=[N-:17])[C@H:10]([OH:11])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 8857Ethyl AcetateHCID 33557Sodium AzideHCID 21991116tert-Butyl 7-Oxa-3-azabicyclo(4.1.0)heptane-3-carboxylate

生成物 1

HCID 58745530(3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester収率 61.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 18366337Propan-2-one--water (1/1)溶媒

反応条件

温度
80 °C

実験手順

To a stirred solution of 7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (15.5 mmol, 3.1 g) in DMF (25 mL) was added a solution of sodium azide (23.3 mmol, 1.5 g) in acetone-water (2:1, 30 mL) (WO 2005/066176). The reaction mixture was heated at 80° C. for 12 h. The reaction mixture was cooled to room temperature, and EtOAc (100 mL) was added. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane) to provide (±)-trans-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (2.3 g)(faster moving compound) 1H NMR (400 MHz, CDCl3) δ 4.12 (1H, dd), 3.95 (1H, bs), 3.50 (1H, bs), 3.30-3.42 (1H, m), 2.90 (1H, bs), 2.79 (1H, dd), 2.30-2.70 (1H, bs), 1.96-2.05 (1H, m), 1.48-1.6 (1H, m), 1.46 (9H, s). and (±)-trans-3-azido-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.57 g) (slower moving compound) 1H NMR (400 MHz, CDCl3) δ 4.21 (1H, bs), 4.00 (1H, d), 3.56 (1H, bs), 3.21-3.35 (1H, m), 2.55-2.95 (2H, m), 2.24 (1H, bs), 1.92-2.04 (1H, m), 1.49-1.6 (1H, m), 1.47 (9H, s)

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane)

出典と根拠

ORDレコード
ord-3e2f7dcc573e4eebbccdc73acf1d199c
出典データセット
uspto-grants-2013_04
特許番号
US08431575B2

反応ノート

読み込み中…