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

HRID 128837

반응식

HRID 128837 반응식
[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

참가 물질

8

반응물 4

HCID 105532-Methyl-2-buteneHCID 3147912-chloro-1H-indole-3-carbaldehydeHCID 516949Sodium Phosphate, Monobasic, Monohydrate2회HCID 23668197Sodium Chlorite2회

생성물 1

HCID 995211H-Indole-3-carboxylic acid, 2-chloro-수율 47.2%

시약·촉매·용매 3

HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
25 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-70d474ac365e439682e399d5b4cd896f
출처 데이터셋
uspto-grants-1995_11
특허 번호
US05464861

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