Epibromohydrin → 3-[(S)-(4-chlorophenyl)(3-hydroxyazetidin-1-yl)methyl]benzonitrile

HRID 602972노트

반응식

HRID 602972 반응식
Cl.Cl[CH2:3][CH:4]([OH:23])[CH2:5][NH:6][C@@H:7]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[C:11]#[N:12].C([O-])(O)=O.[Na+].C(C1OC1)Br>C(O)(C)C>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C@H:7]([N:6]2[CH2:5][CH:4]([OH:23])[CH2:3]2)[C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[C:11]#[N:12])=[CH:17][CH:18]=1

참가 물질

5

반응물 3

HCID 18430EpibromohydrinHCID 516892Sodium BicarbonateHCID 670553393-[(S)-[(3-chloro-2-hydroxypropyl)amino](4-chlorophenyl)methyl]benzonitrile hydrochloride

생성물 1

HCID 576121723-[(S)-(4-chlorophenyl)(3-hydroxyazetidin-1-yl)methyl]benzonitrile

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

To a mixture of 20.27 g (72.6 mmole) of 3-[(S)-[(3-chloro-2-hydroxypropyl)amino](4-chlorophenyl)methyl]benzonitrile hydrochloride and 21.3 g (245 mmole) of NaHCO3 in 600 mL of isopropanol was added 14.4 mL (174 mmole) of epibromohydrin . The mixture was heated to reflux for 24 h, then was cooled and concentrated. The residue was partitioned between 750 mL portions of ether and water and the aqueous layer was washed with two 500 mL portions of ether. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography using 10-20% ethyl acetate in hexane to afford the title compound as a clear oil; 1H-NMR(CDCl3) δ 1.6 (s, 2H, br), 5.24 (s, 1H), 7.24-7.78 (m, 8H).2.89 (m, 2H), 3.54 (m, 2H), 4.39 (s, 1H), 4.52 (m, 1H), 7.2-7.8 (m, 8H).

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 24 h
  3. temperaturewas cooled
  4. concentrationconcentrated
  5. customThe residue was partitioned between 750 mL portions of ether and water
  6. washthe aqueous layer was washed with two 500 mL portions of ether
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-25e24121dc76486aaea64b73662b309f
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906652B2

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