4-Chlorobutyronitrile → 5-[(4-Fluorophenyl)methyl]-3,4-dihydro-2H-pyrrole

HRID 586615Notes

Reaction equation

HRID 586615 reaction equation
[Mg].[F:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1.Cl[CH2:12][CH2:13][CH2:14][C:15]#[N:16]>C(OCC)C>[F:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][C:15]2[CH2:14][CH2:13][CH2:12][N:16]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 123364-ChlorobutyronitrileHCID 680214-Fluorobenzyl bromide2×HCID 5462224Magnesium

Product 1

HCID 139464605-[(4-Fluorophenyl)methyl]-3,4-dihydro-2H-pyrroleYield 37.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Magnesium turnings (for Grignard, 6.4 g, 0.266 mol) are covered with a layer of 20 ml of a solution of 4-fluorobenzyl bromide (50 g, 0.265 mol) in abs. (absolute) diethyl ether (250 ml) in a 500 ml three-necked flask and the mixture is briefly heated until the reaction starts. The remaining volume of 4-fluorobenzyl bromide is added dropwise in the course of 30 min and at the same time the mixture is kept at a temperature of 40° C. for a further 2 h in an oil bath. A solution of 4-chlorobutyronitrile (13.6 g, 0.132 mol) in diethyl ether (50 ml) is added dropwise in the course of 30 min to the still warm, freshly prepared Gringnard solution. The largest part of the ether (200 ml) is distilled off over a bridge and replaced by abs. toluene (250 ml). Diethyl ether is driven off until a boiling temperature of 95° C. is achieved in the bottom. The mixture is stirred at this temperature for a further 2 h and then allowed to stand at RT overnight. The organic phase is transferred to a separating funnel and hydrolysed and extracted with 10% strength HCl (3×100 ml each). The toluene phase is discarded, and the HCl-acidic aqueous phase is again washed with toluene (100 ml) and then maintained at pH 10 using conc. NaOH (32% strength). The pyrroline base depositing is taken up with diethyl ether (100 ml) in the separating funnel. After separating the ether phase, the mixture is again extracted with ether (2×50 ml), and the combined ether phases are dried over K2CO3 sicc. and concentrated. 8.8 g of 2-(4-fluorobenzyl)-1-pyrroline (37.8% based on chloronitrile) are obtained.

Workup

  1. temperaturestill warm
  2. distillationThe largest part of the ether (200 ml) is distilled off over a bridge
  3. waitto stand at RT overnight
  4. customThe organic phase is transferred to a separating funnel
  5. extractionhydrolysed and extracted with 10% strength HCl (3×100 ml each)
  6. washthe HCl-acidic aqueous phase is again washed with toluene (100 ml)
  7. temperaturemaintained at pH 10
  8. customAfter separating the ether phase
  9. extractionthe mixture is again extracted with ether (2×50 ml)
  10. dry with materialthe combined ether phases are dried over K2CO3 sicc
  11. concentrationand concentrated

Sources & evidence

ORD record
ord-bc08b67010714ef4b0644c3d3814e43b
Source dataset
uspto-grants-2005_08
Patent number
US06936632B2

Reaction notes

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