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

HRID 2220313Notes

Reaction equation

HRID 2220313 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, dried MgSO4) and the solvent
  6. customremoved in vacuo
  7. customto give an oil
  8. customThis was purified by flash chromatography with a gradient of 0-30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7bce19b13ab5425aa841897035a7387d
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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