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

HRID 603006ノート

反応式

HRID 603006 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5ab861e0475e4a998b1e9288d89beb1c
出典データセット
uspto-grants-2011_03
特許番号
US07906652B2

反応ノート

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