2,3-Dihydroxybutanedioic Acid → 4-fluoro-1H-indazole-5-carbaldehyde

HRID 218475

반응식

HRID 218475 반응식
[F:1][C:2]1[C:10]([C:11]#N)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[H-].C([Al+]CC(C)C)C(C)C.C(OCC)(=[O:25])C.C(O)(=O)C(C(C(O)=O)O)O>C1(C)C=CC=CC=1>[F:1][C:2]1[C:10]([CH:11]=[O:25])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2

참가 물질

6

반응물 4

HCID 8752,3-Dihydroxybutanedioic AcidHCID 8857Ethyl AcetateHCID 21225700DiisobutylaluminumhydrideHCID 222606314-fluoro-1H-indazole-5-carbonitrile

생성물 1

HCID 249587444-fluoro-1H-indazole-5-carbaldehyde수율 92.9%

시약·촉매·용매 1

HCID 1140Toluene용매2회

반응 조건

온도
-40 °C

실험 절차

805 mg (5 mmols) 4-fluoro-1H-indazole-5-carbonitrile (see EP 1510516, Example 85) were suspended in 25 mL toluene and cooled to −40° C. During 15 minutes 8 mL of a 1.5 M solution of diisobutylaluminium hydride in toluene (12 mmols) were added dropwise. The mixture was stirred for 2 hours at −40° C. At this temperature 5 mL ethyl acetate were added and the mixture was stirred for 20 minutes. 5 mL of a 1 M aqueous solution of tartaric acid were added and the mixture was stirred for 30 minutes at −20 to 0° C. The insolubles were removed by filtration. A small amount of dilute aqueous citric acid was added and the mixture was extracted with ethyl acetate. The extracts were washed with saturated sodium chloride and sodium hydrogen carbonate solutions and dried over sodium sulfate. The crude product was purified with column chromatography to yield 4-fluoro-1H-indazole-5-carbaldehyde 762 mg (92.9%). 1H-NMR (DMSO-d6): 13.82 (br s, 1H); 10.32 (s, 1H); 8.44 (s, 1H); 7.74 (dd, 1H); 7.49 (d, 1H) ppm.

후처리

  1. stirringthe mixture was stirred for 20 minutes
  2. stirringthe mixture was stirred for 30 minutes at −20 to 0° C
  3. customThe insolubles were removed by filtration
  4. additionA small amount of dilute aqueous citric acid was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extracts were washed with saturated sodium chloride and sodium hydrogen carbonate solutions
  7. dry with materialdried over sodium sulfate
  8. customThe crude product was purified with column chromatography

출처 및 근거

ORD 기록
ord-45b134cf0f324cb1b692e2563c278e2c
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198456B2

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