2-Methyl-2-butene → 1H-Indole-3-carboxylic acid, 2-chloro-

HRID 743168

Reaktionsgleichung

Reaktionsgleichung von HRID 743168
[Cl:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.CC(=CC)C.Cl([O-])=[O:19].[Na+].O.P([O-])(O)(O)=O.[Na+]>O.C(OCC)(=O)C.O1CCOCC1>[Cl:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]([OH:19])=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2

Komponenten

8

Edukt 4

HCID 105532-Methyl-2-buteneHCID 3147912-chloro-1H-indole-3-carbaldehydeHCID 516949Sodium Phosphate, Monobasic, Monohydrate2×HCID 23668197Sodium Chlorite2×

Produkt 1

HCID 995211H-Indole-3-carboxylic acid, 2-chloro-Ausbeute 47,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A mechanically stirred suspension of 15 g (83.5 mmol) of 2-chloroindole-3-carboxaldehyde [XXVI: R1 =R3 =H, X=Cl] (Schule, et al., Arch. Pharm. [Weinheim] 1972;305:523-533), 84 mL of 2-methyl-2-butene, and 200 mL of p-dioxane in an ice bath was treated with a solution of 40 g each of sodium chlorite and sodium dihydrogen phosphate monohydrate in 200 mL of water. The biphasic mixture was then stirred vigorously at 25° C. for 3.5 hours. An additional 16 g each of solid sodium chlorite and sodium dihydrogen phosphate monohydrate was added and the mixture was stirred for another 3.5 hours. The mixture was diluted with 350 mL of ethyl acetate and 200 mL of water. The layers were separated and the aqueous phase was extracted with 300 mL of ethyl acetate. The combined organic extracts were extracted with cold 2% aqueous NaOH (3×200 mL). The basic extracts were combined and acidified to pH 4 with 6N aqueous HCl. The precipitated solids were collected by filtration, washed well with water, and air dried overnight. The solids were dissolved in 150 mL of hot acetone and the solution was treated with 65 mL of hexane. After storage at 3° C. for 20 hours, the solids were collected by filtration, washed with cold acetone, and dried to leave 7.71 g of pure 2-chloroindole-3-carboxylic acid [XXVII: R1 =R3 =H, X=Cl] as an off-white solid; mp 181.5° C. (dec). Further processing of the filtrate as above afforded 2.41 g of a second crop; mp 179.5° C. (dec). Total yield 10.12 g (62%).

Aufarbeitung

  1. stirringthe mixture was stirred for another 3.5 hours
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with 300 mL of ethyl acetate
  4. extractionThe combined organic extracts were extracted with cold 2% aqueous NaOH (3×200 mL)
  5. filtrationThe precipitated solids were collected by filtration
  6. washwashed well with water, and air
  7. customdried overnight
  8. dissolutionThe solids were dissolved in 150 mL of hot acetone
  9. additionthe solution was treated with 65 mL of hexane
  10. waitAfter storage at 3° C. for 20 hours
  11. filtrationthe solids were collected by filtration
  12. washwashed with cold acetone
  13. customdried

Quellen und Nachweise

ORD-Eintrag
ord-aee63ddfe7ce4dbd88c827e421cf78a7
Quelldatensatz
uspto-grants-1996_09
Patentnummer
US05556874

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