Hydrochloric Acid → ethyl 1-tosyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 523466ノート

反応式

HRID 523466 の反応式
[S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[Li]CCCC.[C:25](Cl)(=[O:29])[O:26][CH2:27][CH3:28].Cl>C1COCC1.O>[S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[C:12]1[C:25]([O:26][CH2:27][CH3:28])=[O:29])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 679757621-tosyl-1H-pyrrolo[3,2-c]pyridineHCID 178418339Butyllithium

生成物 1

HCID 67975542ethyl 1-tosyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of compound 6-b (10 g, 367 mmol) in dry THF (150 mL) was cooled to −70° C. and n-BuLi (CAS 109-72-8) (2.5 M in hexane, 16.7 mL, 41.9 mmol) was added dropwise under N2. The mixture was stirred at −78° C. for 1 hour and then ethyl carbonochloridate (CAS 541-41-3) (fresh redistilled, 4.2 mL, 44 mmol) was added dropwise at −70° C. The mixture was warmed to 20° C. naturally and stirred at 20° C. for 1 hour. Then water (800 mL) was added. The mixture was acidified to pH=4 to 5 with a 1N HCl aqueous solution and extracted with ethyl acetate (400 mL×2). Then the pH of the aqueous layer was adjusted to pH=8 by addition of NaHCO3. The resulting mixture was extracted with ethyl acetate (200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was washed with tert-butylmethyl ether. The solid was dried under high vacuum. The residue was purified by flash column chromatography, eluting with petroleum ether/ethyl acetate (3:2). After evaporation of the fractions, 6-c is obtained (6 g, 47%).

後処理

  1. temperatureThe mixture was warmed to 20° C. naturally
  2. stirringstirred at 20° C. for 1 hour
  3. extractionextracted with ethyl acetate (400 mL×2)
  4. additionThen the pH of the aqueous layer was adjusted to pH=8 by addition of NaHCO3
  5. extractionThe resulting mixture was extracted with ethyl acetate (200 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. washThe residue was washed with tert-butylmethyl ether
  10. customThe solid was dried under high vacuum
  11. customThe residue was purified by flash column chromatography
  12. washeluting with petroleum ether/ethyl acetate (3:2)
  13. customAfter evaporation of the fractions

出典と根拠

ORDレコード
ord-b78bae880a6a49c78ec77f0c2a3fa726
出典データセット
uspto-grants-2016_05
特許番号
US09339494B2

反応ノート

読み込み中…