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

HRID 402083노트

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HRID 402083 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 18366337Propan-2-one--water (1/1)용매

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온도
80 °C

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-3904210fddd44fb082f2cbc4762be9f6
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741900B2

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