p-Toluenesulphonyl cyanide → 7-Methoxy-1-benzothiophene-2-carbonitrile

HRID 1822966Notes

Reaction equation

HRID 1822966 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[S:10][CH:9]=[CH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.C([Li])CCC.S([C:27]#[N:28])(C1C=CC(C)=CC=1)(=O)=O>C1COCC1>[CH3:1][O:2][C:3]1[C:11]2[S:10][C:9]([C:27]#[N:28])=[CH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 87946p-Toluenesulphonyl cyanideHCID 110842177-Methoxybenzo[b]thiopheneHCID 178418339Butyllithium

Product 1

HCID 131232427-Methoxy-1-benzothiophene-2-carbonitrileYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-benzothien-7-yl methyl ether (1 g, 6.1 mmol) in THF (12 mL) at −78° C. was added a solution of 2.5 M n-butyllithium in hexanes (2.9 mL, 7.3 mmol). After stirring for 1.5 hr this solution was added dropwise to a solution of tosyl cyanide (1.66 g, 9.1 mmol) in THF (8 mL), this was left stirring at −78° C. for 0.5 hr and then warmed to room temperature. After 16 h this was poured onto ice-water and extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with water, dried (MgSO4) and the solvent removed in vacuo to give an oil. This was purified by flash chromatography with a gradient of 0–30% ethyl acetate in hexane to give the title compound (0.31 g, 27%); δH (300 MHz, CDCl3) 7.79 (1H, s, 3-ArH), 7.46–7.38 (1H, m, 4-ArH), 7.37–7.31 (1H, m, 5-ArH), 6.88–6.82 (1H, m, 6-ArH) and 3.94 (3H, s, OCH3). Starting material 1-benzothien-7-yl methyl ether was recovered from the reaction (0.56 g, 56%); δH (300 MHz, CDCl3) 7.45–7.29 (4H, m, ArH), 6.75 (1H, m, ArH), 4.00 (3H, s, OCH3).

Workup

  1. waitthis was left
  2. stirringstirring at −78° C. for 0.5 hr
  3. additionAfter 16 h this was poured onto ice-water
  4. extractionextracted with dichloromethane (3×50 mL)
  5. washThe combined organic extracts were washed with water
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customto give an oil
  9. customThis was purified by flash chromatography with a gradient of 0–30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-8005c00fb06d4e5fbf2a47d4aba5fe4a
Source dataset
uspto-grants-2006_05
Patent number
US07037932B2

Reaction notes

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