Pyridine-2-carbonitrile → [2-(2-Benzyloxy-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanone

HRID 746625Notes

Reaction equation

HRID 746625 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(CCN(C)C)C.[Li]C(CC)C.[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)#N.C1C[O:45]CC1>C1(C)C=CC=CC=1>[CH2:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)=[O:45])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 7522Pyridine-2-carbonitrileHCID 8028TetrahydrofuranHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 585915582-(2-Benzyloxy-ethyl)-3-bromo-benzo[b]thiopheneHCID 178418400CID 53628100

Product 1

HCID 58591577[2-(2-Benzyloxy-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanoneYield 41%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a cooled solution (−78° C.) of 2-(2-benzyloxy-ethyl)-3-bromo-benzo[b]thiophene (9.6 g, 27.6 mmol) in anhydrous THF (200 mL), TMEDA (4.14 mL, 27.6 mmol) was added and the mixture was stirred for 5 min. After dropwise addition of sec-BuLi (23.3 mL, 30.3 mmol), while keeping the temperature below −60° C., the mixture was stirred for an additional 30 min at −78° C. A solution of 2-cyanopyridine (3.16 g, 30.34 mmol) in toluene (30 mL) was added and after stirring for 30 min at −78° C. the reaction was quenched by dropwise addition of 6N HCl (66 mL) in MeOH (134 mL), while keeping the temperature below −60° C. After stirring overnight while allowing the mixture to reach room temperature, the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and NH4OH (100 mL) was added. The organic layer was separated and the aqueous layer was further extracted with dichloromethane. The combined organic layers were dried (Na2SO4), concentrated and subjected to silica gel column chromatography (eluent: EtOAc/Hex=1/4 up to EtOAc/Hex=1/1) to afford 4.2 g of [2-(2-benzyloxy-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanone (41% yield).

Workup

  1. customthe temperature below −60° C.
  2. stirringthe mixture was stirred for an additional 30 min at −78° C
  3. stirringafter stirring for 30 min at −78° C. the reaction
  4. customwas quenched by dropwise addition of 6N HCl (66 mL) in MeOH (134 mL)
  5. customthe temperature below −60° C
  6. stirringAfter stirring overnight
  7. customto reach room temperature
  8. concentrationthe mixture was concentrated in vacuo
  9. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  10. additionNH4OH (100 mL) was added
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was further extracted with dichloromethane
  13. dry with materialThe combined organic layers were dried (Na2SO4)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-480a6b70c88a4f7dac8ea74f37a06db5
Source dataset
uspto-grants-2008_07
Patent number
US07393865B2

Reaction notes

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