Dimethylformamide → 6-Fluoro-1-methyl-1H-indazole-5-carbaldehyde

HRID 1942052ノート

反応式

HRID 1942052 の反応式
C([Mg]Cl)CCC.C([Li])CCC.CCCCCC.Br[C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][C:27]=1[F:28])[N:24]([CH3:29])[N:23]=[CH:22]2.CN([CH:33]=[O:34])C>C1COCC1.C1(C)C=CC=CC=1>[F:28][C:27]1[CH:26]=[C:25]2[C:21]([CH:22]=[N:23][N:24]2[CH3:29])=[CH:20][C:19]=1[CH:33]=[O:34]

参加物

8

反応物 5

HCID 6228DimethylformamideHCID 8058HexaneHCID 579172745-Bromo-6-fluoro-1-methyl-1H-indazoleHCID 178418265HCID 178418265、化合物HCID 178418339Butyllithium

生成物 1

HCID 579174476-Fluoro-1-methyl-1H-indazole-5-carbaldehyde

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

A 2 M solution of n-butyl magnesium chloride in THF (22.4 mL, 44.8 mmol) was added to toluene (160 mL) under nitrogen and cooled to −10° C. To this was added a 1.6 M solution of n-butyl lithium in hexane (57 mL, 91 mmol) and after 1 h, the RM was cooled to −30° C. To the RM was then added a solution of 5-bromo-6-fluoro-1-methyl-1H-indazole ((v) 19.0 g, 83 mmol) in THF (160 mL) and the reaction was warmed up to −10° C. After 1 h, DMF (8.23 mL, 106 mmol) was added and the RM was stirred at −10° C. for another 1 h. The reaction was quenched using 2 N HCl and was allowed to warm up to room temperature. After 30 min, the RM was basified with saturated aqueous NaHCO3 solution and then extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated under vacuo. The residue was triturated with Et2O. The precipitate formed was filtered off to give a beige solid identified as the desired aldehyde (tR 3.61 min (conditions 1), NMR in DMSO-d6: 10.16 (s, 1H); 8.36 (d, 1H); 8.30 (s, 1H); 7.70 (d, 1H); 4.03 (s, 3H)).

後処理

  1. temperaturethe RM was cooled to −30° C
  2. temperaturethe reaction was warmed up to −10° C
  3. waitAfter 1 h
  4. customThe reaction was quenched
  5. temperatureto warm up to room temperature
  6. waitAfter 30 min
  7. extractionextracted with EtOAc
  8. washThe organic phase was washed with brine
  9. dry with materialdried over Na2SO4
  10. customevaporated under vacuo
  11. customThe residue was triturated with Et2O
  12. customThe precipitate formed
  13. filtrationwas filtered off
  14. customto give a beige solid

出典と根拠

ORDレコード
ord-4830791264c14a6c91dcb559c75aabca
出典データセット
uspto-grants-2013_03
特許番号
US08389526B2

反応ノート

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