Acetonitrile → [4-(3-Pyrrolidin-1-ylpropoxy)phenyl]acetonitrile

HRID 1866542Notes

Reaction equation

HRID 1866542 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[OH:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#N)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:25](#[N:27])C>>[N:5]1([CH2:4][CH2:3][CH2:2][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH2:15][C:25]#[N:27])=[CH:13][CH:12]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 130194-CyanophenolHCID 113210281-(3-Chloropropyl)-pyrrolidine

Product 1

HCID 23091635[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]acetonitrileYield 79%

Conditions

Temperature
45 °C

Procedure

A mixture of 1-(3-chloropropyl)pyrrolidine (J. Am. Chem. Soc., 77, 2270; 1955) (133 g, 0.9 mol), 4-hydroxybenzonitrile (100 g, 0.75 mol) and caesium carbonate (256 g, 0.78 mol) in acetonitrile (1 L) was stirred at 45° C. for 18 hours. The reaction mixture was then concentrated in vacuo and the residue was partitioned between ethyl acetate (800 mL) and water (800 mL). The aqueous layer was separated and extracted with ethyl acetate (800 mL) and the combined organic solution was washed with water (500 mL) and extracted with 2M hydrochloric acid (2×600 mL). The acidic solution was basified to pH8-9 with 40% potassium hydroxide solution and extracted with ethyl acetate (800 mL). The aqueous solution was then further basified to pH10-11 using 40% potassium hydroxide solution and extracted with ethyl acetate (800 mL). The combined organic solution was dried over sodium sulfate, filtered through a pad of silica and concentrated in vacuo to afford the title compound as a red oil in 79% yield, 150 g. 1H NMR (400 MHz, CDCl3) δ: 7.24 (2H, d), 6.85 (2H, d), 4.09-3.89 (2H, m), 3.75 (2H, s), 2.71-2.36 (6H, m), 2.14-1.93 (2H, m), 1.89-1.65 (4H, m) ppm; LRMS APCI m/z 245 [M+H]+

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate (800 mL) and water (800 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (800 mL)
  5. washthe combined organic solution was washed with water (500 mL)
  6. extractionextracted with 2M hydrochloric acid (2×600 mL)
  7. extractionextracted with ethyl acetate (800 mL)
  8. extractionextracted with ethyl acetate (800 mL)
  9. dry with materialThe combined organic solution was dried over sodium sulfate
  10. filtrationfiltered through a pad of silica
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-337d48ccb0af45e8ae6d6bf654a58fde
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

Loading…