Dimethylacetamide → 2-Cyano-6-methoxyisonicotinic acid

HRID 931081ノート

反応式

HRID 931081 の反応式
Cl[C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([O:13][CH3:14])[N:12]=1)[C:5]([O:7]CC)=[O:6].[CH3:15][N:16](C)C(=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:15]([C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([O:13][CH3:14])[N:12]=1)[C:5]([OH:7])=[O:6])#[N:16]

参加物

6

反応物 2

HCID 31374DimethylacetamideHCID 13611989Ethyl 2-chloro-6-methoxyisonicotinate

生成物 1

HCID 722157132-Cyano-6-methoxyisonicotinic acid収率 45.3%

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 178418851HCID 178418851、化合物触媒

反応条件

温度
95 °C

実験手順

Into an oven-dried microwave vial was added ethyl 2-chloro-6-methoxyisonicotinate (0.6 g, 2.78 mmol), zinc cyanide (392 mg, 3.34 mmol), zinc dust (36.4 mg, 0.2 mmol) and N,N-dimethylacetamide (10 mL). The vial was capped, evacuated, and filled with nitrogen. This process was repeated 3 times. Then the cap of the vial was removed and bis(tri-t-butylphosphine)palladium(0) (142 mg, 0.278 mmol) was added. The vial was capped again, evacuated, and filled with nitrogen (3×). The reaction mixture was heated to 95° C. and left stirring for 18 h. The reaction mixture was diluted with ethyl acetate (100 mL) and filtered through Celite. The filtrate was poured into a saturated aqueous solution of sodium bicarbonate (100 mL). Then the mixture was extracted with ethyl acetate (50 mL×3). The combined organics were washed with a saturated aqueous solution of ammonium chloride, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified via flash chromatography to afford 2-cyano-6-methoxyisonicotinic acid (260 mg, 45.3%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 4.01 (s, 3H), 4.43 (s, 2H), 7.53 (s, 1H), 7.82 (s, 1H).

後処理

  1. customThe vial was capped
  2. customevacuated
  3. additionfilled with nitrogen
  4. customThen the cap of the vial
  5. customwas removed
  6. customThe vial was capped again
  7. customevacuated
  8. additionfilled with nitrogen (3×)
  9. waitleft
  10. additionThe reaction mixture was diluted with ethyl acetate (100 mL)
  11. filtrationfiltered through Celite
  12. additionThe filtrate was poured into a saturated aqueous solution of sodium bicarbonate (100 mL)
  13. extractionThen the mixture was extracted with ethyl acetate (50 mL×3)
  14. washThe combined organics were washed with a saturated aqueous solution of ammonium chloride
  15. washwashed with brine
  16. dry with materialdried over sodium sulfate
  17. customThe solvent was removed under reduced pressure
  18. customthe residue was purified via flash chromatography

出典と根拠

ORDレコード
ord-b1ab5088b4ec430cbd7238b196b4230e
出典データセット
uspto-grants-2016_03
特許番号
US09296745B2

反応ノート

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