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

HRID 746625ノート

反応式

HRID 746625 の反応式
[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

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-480a6b70c88a4f7dac8ea74f37a06db5
出典データセット
uspto-grants-2008_07
特許番号
US07393865B2

反応ノート

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