Tetrahydrofuran → HCID 12859835, compound

HRID 232308Notes

Reaction equation

HRID 232308 reaction equation
[CH2:1]([N:3]([CH2:8][CH3:9])[CH2:4][CH2:5][CH2:6]Cl)[CH3:2].[Mg].C([Mg]Br)C.[F:15][C:16]1[CH:23]=[CH:22][C:19]([C:20]#N)=[CH:18][CH:17]=1.[O:24]1CCCC1>C(OCC)C>[CH2:1]([N:3]([CH2:8][CH3:9])[CH2:4][CH2:5][CH2:6][C:20]([C:19]1[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=1)=[O:24])[CH3:2]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 145174-FluorobenzonitrileHCID 669183-Chloropropyl(diethyl)amineHCID 5462224MagnesiumHCID 178418443HCID 178418443, compound

Product 1

HCID 12859835HCID 12859835, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of 73.1 g (0.489 mol) 3-(diethylamino)-propyl chloride and 11.87 g (0.489 mol) of magnesium in 300 mL of tetrahydrofuran is initiated with 0.25 mL of 3M ethylmagnesium bromide in diethyl ether and is refluxed overnight. After this time, the reaction is allowed to cool to 40° C. and is treated with 29.6 g (0.245 mol) of 4-fluorobenzonitrile. The initial exotherm is followed by applied heat and the reaction is refluxed for 3 hr. After this time, the reaction is allowd to cool to room temperature and is quenched with 250 mL of water. This mixture is extracted with 2×250 mL of methylene chloride. The combined organic layers are acidifed to pH=1 with 2N aq. hydrochloric acid and the resulting layers separated. The aqueous extract is washed with 100 mL of methylene chloride and is made basic with 4N of sodium hydroxide. The aqueous mixture is extracted with 3×300 mL of methylene chloride. The combined organic layers are dried over sodium sulfate, filtered and the solvent distilled in vacuo to provide crude title compound. This liquid is distilled under vacuum to provide the title compound.

Workup

  1. temperatureis refluxed overnight
  2. temperatureby applied heat
  3. temperaturethe reaction is refluxed for 3 hr
  4. temperatureto cool to room temperature
  5. customis quenched with 250 mL of water
  6. extractionThis mixture is extracted with 2×250 mL of methylene chloride
  7. customthe resulting layers separated
  8. extractionThe aqueous extract
  9. washis washed with 100 mL of methylene chloride
  10. extractionThe aqueous mixture is extracted with 3×300 mL of methylene chloride
  11. dry with materialThe combined organic layers are dried over sodium sulfate
  12. filtrationfiltered
  13. distillationthe solvent distilled in vacuo
  14. customto provide crude title compound
  15. distillationThis liquid is distilled under vacuum

Sources & evidence

ORD record
ord-e531af4e4b514897b65f408413590bed
Source dataset
uspto-grants-1989_07
Patent number
US04851526

Reaction notes

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