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

HRID 602658Notes

Reaction equation

HRID 602658 reaction equation
Cl[CH2:2][CH:3]([OH:22])[CH2:4][NH:5][C@@H:6]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=1)[C:10]#[N:11].C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@H:6]([N:5]2[CH2:4][CH:3]([OH:22])[CH2:2]2)[C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=2)[C:10]#[N:11])=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 670553403-[(S)-[(3-chloro-2-hydroxypropyl)amino](4-chlorophenyl)methyl]benzonitrile

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 8.0 g (24.0 mmole) of 3-[(S)-[(3-chloro-2-hydroxypropyl)amino](4-chlorophenyl)methyl]benzonitrile and 11.7 g (36 mmole) of Cs2CO3 in 50 mL of dry CH3CN was divided between two 80 mL microwave tubes. The tubes were irradiated in a microwave oven (with coolin) at 160° C. for 8 h. The samples were filtered and the solids were washed with 20 mL of CH3CN and then 20 mL of CH2Cl2. The combined filtrates were concentrated and the residue was portioned between 300 mL ethyl acetate and 100 mL water. The layers were separated and the aqueous layer was washed with 100 mL ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography using 10-20% ethyl acetate in CH2Cl2 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. customThe tubes were irradiated in a microwave oven (with coolin) at 160° C. for 8 h
  2. filtrationThe samples were filtered
  3. washthe solids were washed with 20 mL of CH3CN
  4. concentrationThe combined filtrates were concentrated
  5. customThe layers were separated
  6. washthe aqueous layer was washed with 100 mL ethyl acetate
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-c8a7bb3d0a5b4c679b5f298a2939c78e
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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