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

HRID 602972Notes

Reaction equation

HRID 602972 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-25e24121dc76486aaea64b73662b309f
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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