Hydrochloric Acid → 2-[(4-Fluorophenyl)methyl]thiophene

HRID 233129Notes

Reaction equation

HRID 233129 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[S:5]1[CH:9]=[CH:8][CH:7]=[C:6]1[C:10](Cl)=O.Cl.[BH4-].[Na+].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>COCCOCCOC.O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:10][C:6]2[S:5][CH:9]=[CH:8][CH:7]=2)=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10008Fluorobenzene3×HCID 789282-Thiophenecarbonyl chlorideHCID 4311764Sodium borohydrideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 105839052-[(4-Fluorophenyl)methyl]thiopheneYield 75.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8150DiglymeSolvent

Conditions

Temperature
0 °C

Procedure

33.8 g of aluminium chloride were suspended in 200 g of fluorobenzene, and a solution of 37.8 g of thiophene-2-carbonyl chloride in 50 ml of fluorobenzene was added dropwise to this at 0° C. over the course of 30 minutes. The mixture was stirred at 0° C. for 2 hours and then slowly warmed, and heated under reflux at 85° C. for 2 hours until evolution of hydrogen chloride ceased. The solution was cooled to 70° C. and then, at this temperature, added dropwise over the course of 30 minutes to a stirred suspension of 7.2 g of of sodium borohydride in 50 ml of diglyme. The mixture was then stirred at 70° C. for 90 minutes and, after cooling, discharged into a mixture of 250 g of ice, 200 ml of water and 62.5 g of concentrated aqueous hydrochloric acid. After addition of 100 ml of fluorobenzene, the organic phase was separated off, extracted by shaking with 100 ml of water and concentrated. Yield: 58.3 g of product with a content of 61.8% by weight of 2-(4-fluorobenzyl)thiophene (GC), corresponding to a yield of 75.1% of theory. An organic phase was obtained from the aqueous mother liquor by extraction with methylene chloride and concentration and contained a further 33.7% by weight of the required product (GC), corresponding to an additional yield of 4.6% of theory. Distillation of the organic phase resulted in a 99.2% pure 2-(4-fluorobenzyl)thiophene.

Workup

  1. temperatureslowly warmed
  2. temperatureheated
  3. temperatureThe solution was cooled to 70° C.
  4. stirringThe mixture was then stirred at 70° C. for 90 minutes
  5. temperatureafter cooling
  6. customthe organic phase was separated off
  7. extractionextracted
  8. stirringby shaking with 100 ml of water
  9. concentrationconcentrated
  10. customAn organic phase was obtained from the aqueous mother liquor by extraction with methylene chloride and concentration

Sources & evidence

ORD record
ord-9bf37336c2944d3d8f504448f0d028b1
Source dataset
uspto-grants-1997_01
Patent number
US05591869

Reaction notes

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