Phosphorus oxychloride → 6,7-Dihydrobenzo[b]thiophene-4-carbonitrile

HRID 2183612Notes

Reaction equation

HRID 2183612 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[C:6](=O)[CH2:7][CH2:8][CH2:9][C:2]1=2.C[Si]([C:15]#[N:16])(C)C.P(Cl)(Cl)(Cl)=O>B(F)(F)F.CCOCC.N1C=CC=CC=1>[S:1]1[CH:5]=[CH:4][C:3]2[C:6]([C:15]#[N:16])=[CH:7][CH2:8][CH2:9][C:2]1=2

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 82115Trimethylsilyl cyanideHCID 834184,5,6,7-Tetrahydro-4-oxothionaphthene

Product 1

HCID 224741326,7-Dihydrobenzo[b]thiophene-4-carbonitrileYield 63.9%

Reagents, catalysts & solvents 2

HCID 8000Boron trifluoride etherateCatalystHCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

Boron trifluoride diethyl etherate (120 drops) was added dropwise under nitrogen at ambient temperature to a stirred mixture of 6,7-dihydrobenzo[b]thiophen-4(5H)-one (130.5 g) and trimethylsilyl cyanide (98 g), the mixture was stirred at ambient temperature for 2 hours and at 100° C. for 1 hour, then it was allowed to stand at ambient temperature for 18 hours. Pyridine (650 ml) followed by phosphorus oxychloride (125 ml) were added, the mixture was heated at 140° C. for 2 hours whilst volatile materials were removed by distillation, then it was cooled to ambient temperature and added to crushed ice (2000 ml). Ether (2000 ml) was added and the mixture was filtered through Celite. The filter pad was washed with ether (500 ml), the aqueous phase was separated, and further product was extracted from it using ether (500 ml). The ethereal solutions were combined, washed with water (500 ml), 5M hydrochloric acid (2250+500 ml), water (500 ml) and saturated aqueous sodium chloride solution (500 ml), then they were dried (MgSO4) and the solvents were removed in vacuo to give crude 6,7-dihydrobenzo[b]thiophene-4-carbonitrile (88.3 g) as an orange oil which was used without further purification.

Workup

  1. waitto stand at ambient temperature for 18 hours
  2. additionwere added
  3. temperaturethe mixture was heated at 140° C. for 2 hours whilst volatile materials
  4. customwere removed by distillation
  5. temperatureit was cooled to ambient temperature
  6. additionadded
  7. customto crushed ice (2000 ml)
  8. additionEther (2000 ml) was added
  9. filtrationthe mixture was filtered through Celite
  10. washThe filter pad was washed with ether (500 ml)
  11. customthe aqueous phase was separated
  12. extractionfurther product was extracted from it
  13. washwashed with water (500 ml), 5M hydrochloric acid (2250+500 ml), water (500 ml) and saturated aqueous sodium chloride solution (500 ml)
  14. dry with materialthey were dried (MgSO4)
  15. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-ad5f12af038348ce8f41c5b45c67e7e9
Source dataset
uspto-grants-2005_05
Patent number
US06900216B2

Reaction notes

Loading…