Bis(2-chloroethyl) ether → 4-(3-Methoxyphenyl)oxane-4-carbonitrile

HRID 272808

Reaction equation

HRID 272808 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]#[N:11])[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].Cl[CH2:15][CH2:16][O:17][CH2:18][CH2:19]Cl>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2([C:10]#[N:11])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 8115Bis(2-chloroethyl) etherHCID 24758Sodium hydrideHCID 88310(3-Methoxyphenyl)acetonitrile

Product 1

HCID 187863664-(3-Methoxyphenyl)oxane-4-carbonitrileYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

3-Methoxyphenylacetonitrile (10 g, 67.9 mmol) in DMF (50 ml) was added slowly to a suspension of NaH (5.04 g, 150 mmol) in DMF (50 ml) at 0° C. under N2. The reaction was allowed to warm to room temperature and stirred for 30 nms. The reaction was cooled to 0° C. and bis(2-chloroethyl)ether (10.7 g, 74.7 mmol) in DMF (100 ml) was added dropwise over 80 min. The reaction was allowed to warm to room temperature and stirred for 1 hour. The reaction was quenched with water (500 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine (3×50 ml), dried over MgSO4, filtered, washed with ethyl acetate and concentrated in vacuo. The crude mixture was purified by column chromatography, eluting with heptane increasing the polarity to heptane:ethyl acetate (90:10), to give 4-(3-methoxyphenyl)tetrahydro-pyran-4-carbonitrile (4.1 g, 28%).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 1 hour
  4. customThe reaction was quenched with water (500 ml)
  5. extractionextracted with ethyl acetate (3×100 ml)
  6. washThe combined organic extracts were washed with brine (3×50 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. washwashed with ethyl acetate
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified by column chromatography
  12. washeluting with heptane increasing the polarity to heptane:ethyl acetate (90:10)

Sources & evidence

ORD record
ord-c0296a5b2e614158a90ed9b8370dbd3d
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Linked notes

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