Hydrochloric Acid → 2-(2-Thien-3-yl-5-pyridyl)propanenitrile

HRID 1358684Notes

Reaction equation

HRID 1358684 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7](Br)=[N:8][CH:9]=1)(=O)[CH3:2].[S:11]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12]1.C(=O)([O-])[O-].[K+].[K+].[C-]#N.[Li+].C(OP([C:36]#[N:37])(=O)OCC)C.[Sm].ICCI.Cl>O1CCOCC1.O.[Cl-].[Na+].O.C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[S:11]1[CH:15]=[CH:14][C:13]([C:7]2[CH:6]=[CH:5][C:4]([CH:1]([CH3:2])[C:36]#[N:37])=[CH:9][N:8]=2)=[CH:12]1

Participants

14

Reactant 8

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 122241,2-DiiodoethaneHCID 23951SamariumHCID 75478Lithium cyanideHCID 76257Diethyl cyanophosphonateHCID 581760Thiophene-3-boronic acidHCID 156681955-Acetyl-2-bromopyridine

Product 1

HCID 218934532-(2-Thien-3-yl-5-pyridyl)propanenitrileYield 22%

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 960 mg (4.8 mmol) of 5-acetyl-2-bromopyridine, 676 mg (5.28 mmol) of thiophene 3-boronic acid, 222 mg (0.19 mmol) of tetrakis(triphenylphosphine) palladium and 995 mg (7.2 mmol)of potasium carbonate in 13 ml of dioxane and 3 ml of water, was heated at 90° C. overnight. Brine was added and extracted three times with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. To a solution of the crude and 475 mg (14.4 mmol) of lithium cyanide in 16 ml of THF, 2.2 ml (14.4 mmol) of diethylcyanophosphonate was added neat at ambient temperature. The mixture was stirred at ambient temperature for 30 min. Water was added and extracted with a 1:1 solution of ethyl acetate/hexane. The organic solution was dried over Na2SO4 filtered and concentrated in vacuo. The crude was disolved in 10 ml of THF and added dropwise to a solution of samarium iodide, prepared from 3.32 g (22.08 mmol) of samarium and 3.89 g (13.8 mmol) of 1,2-diiodoethane. The mixture was stirred for 1 h. A 2.5 N solution of hydrochloric acid was added and extracted three times with diethyl ether. The organic phase was washed with a 1 N solution of sodium thiosulfate. The organic solution was dried over Na2SO4 filtered and concentrated in vacuo. Chromatography (100 g of silica gel, 25% ethyl acetate/hexane) of the residue afforded 225 mg (22%) of the title compound.

Workup

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. extractionextracted with a 1:1 solution of ethyl acetate/hexane
  6. dry with materialThe organic solution was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionadded dropwise to a solution of samarium iodide
  10. stirringThe mixture was stirred for 1 h
  11. extractionextracted three times with diethyl ether
  12. washThe organic phase was washed with a 1 N solution of sodium thiosulfate
  13. dry with materialThe organic solution was dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-007e4f69b86944b78d4716f5067f15bf
Source dataset
uspto-grants-2003_07
Patent number
US06596716B2

Reaction notes

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