Chloroacetaldehyde → Methyl 5-chloroimidazo[1,2-a]pyridine-8-carboxylate

HRID 406275ノート

反応式

HRID 406275 の反応式
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:12])[N:3]=1.C(=O)(O)[O-].[Na+].Cl[CH2:19][CH:20]=O>CO.O>[Cl:12][C:4]1[N:3]2[CH:19]=[CH:20][N:1]=[C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1

参加物

6

反応物 3

HCID 33Chloroacetaldehyde2 回HCID 516892Sodium BicarbonateHCID 57415887Methyl 2-amino-6-chloronicotinate

生成物 1

HCID 86710850Methyl 5-chloroimidazo[1,2-a]pyridine-8-carboxylate収率 58.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a stirred suspension of methyl 2-amino-6-chloro-3-pyridinecarboxylate (2 g, 10.72 mmol) and sodium bicarbonate (900 mg, 10.72 mmol) in a mixture of methanol (40 mL) and water (20 mL) was added chloroacetaldehyde (50% wt. solution in water, 2.9 mL, 22.51 mmol). The resultant mixture was heated at reflux for 5 hours when more chloroacetaldehyde (50% wt. solution in water, 1.45 mL, 11.25 mmol) was added and heating at reflux continued for 16 hours. The majority of the solvent was then removed in vacuo and the residue was partitioned between ethyl acetate (150 mL) and saturated aqueous sodium bicarbonate (150 mL). The organic phase was separated and the aqueous phase was back extracted with ethyl acetate (150 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in DCM and purified on a silica cartridge (100 g) using a 0-100% ethyl acetate-cyclohexane+0-20% methanol gradient over 60 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (1.32 g).

後処理

  1. additionwas added
  2. temperatureheating
  3. temperatureat reflux
  4. customThe majority of the solvent was then removed in vacuo
  5. customthe residue was partitioned between ethyl acetate (150 mL) and saturated aqueous sodium bicarbonate (150 mL)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was back extracted with ethyl acetate (150 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in DCM
  12. custompurified on a silica cartridge (100 g)
  13. waitgradient over 60 mins
  14. customevaporated in vacuo

出典と根拠

ORDレコード
ord-ac69b76078bf4466a27c517e06d71d51
出典データセット
uspto-grants-2014_06
特許番号
US08754101B2

反応ノート

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