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

HRID 1724173Notes

Reaction equation

HRID 1724173 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

Conditions

Temperature
160 °C

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 cooling) 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), 7.27-7.8 (m, 8H).

Workup

  1. customThe tubes were irradiated in a microwave oven
  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-6bb5fd08b3d141448f9063948c9d0aaa
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

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