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

HRID 218475

反応式

HRID 218475 の反応式
[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

参加物

6

反応物 4

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

生成物 1

HCID 249587444-fluoro-1H-indazole-5-carbaldehyde収率 92.9%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
-40 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-45b134cf0f324cb1b692e2563c278e2c
出典データセット
uspto-grants-2012_06
特許番号
US08198456B2

関連ノート

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