Tetrahydrofuran → 4-(3-Fluorophenyl)-1H-pyrrole-3-carbonitrile

HRID 1629977Notes

Reaction equation

HRID 1629977 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]#[N:13])[CH:7]=[CH:8][CH:9]=1.S([CH2:24][N+:25]#[C-])(C1C=CC(C)=CC=1)(=O)=O.O1CCC[CH2:28]1>C(Cl)(Cl)Cl>[F:3][C:4]1[CH:5]=[C:6]([C:10]2[C:11]([C:24]#[N:25])=[CH:12][NH:13][CH:28]=2)[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 367315HCID 367315, compound2×

Product 1

HCID 534262514-(3-Fluorophenyl)-1H-pyrrole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of 19.8 g (494 mmol) of sodium hydride at 60% in oil in 350 ml of anhydrous tetrahydrofuran is added dropwise a mixture of 48.5 g (330 mmol) of the mixture of (Z) and (E) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) and 64.4 g (330 mmol) of tosylmethyl isocyanide (CAS 36635-61-7) dissolved in 250 ml of tetrahydrofuran, while maintaining the temperature of the reaction medium at about 25° C. The mixture is then stirred for 1 hour at room temperature and is then poured into ice-water. The reaction product is then extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown solid, which is dissolved in 350 ml of hot chloroform and purified by chromatography on a column of 600 g of silica gel, eluting with dichloromethane and then with a mixture of 1% methanol in dichloromethane, to give 41.5 g of 4-(3-fluorophenyl)-1H-pyrrole-3-carbonitrile in the form of a beige-coloured solid after triturating in dichloromethane, filtering off and drying.

Workup

  1. additionis added dropwise
  2. extractionThe reaction product is then extracted with ethyl acetate
  3. dry with materialthe organic phase is dried over sodium sulfate
  4. customthe solvent is evaporated off under reduced pressure
  5. customto give a brown solid, which
  6. custompurified by chromatography on a column of 600 g of silica gel
  7. washeluting with dichloromethane
  8. additionwith a mixture of 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-785abbf352e24392a0f78bdf588d55b0
Source dataset
uspto-grants-2014_07
Patent number
US08791119B2

Reaction notes

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