Dimethylformamide → 6-Fluoro-1-tetrahydropyran-2-yl-indazole-4-carbaldehyde

HRID 475312ノート

反応式

HRID 475312 の反応式
C([Li])CCC.Br[C:7]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]2[C:8]=1[CH:9]=[N:10][N:11]2[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1.CN([CH:26]=[O:27])C>C1COCC1>[F:16][C:14]1[CH:15]=[C:7]([CH:26]=[O:27])[C:8]2[CH:9]=[N:10][N:11]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:12]=2[CH:13]=1

参加物

5

反応物 3

HCID 6228DimethylformamideHCID 866947634-Bromo-6-fluoro-1-tetrahydropyran-2-yl-indazoleHCID 178418339Butyllithium

生成物 1

HCID 866947626-Fluoro-1-tetrahydropyran-2-yl-indazole-4-carbaldehyde収率 66%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

To a solution of n-butyllithium (13 mL, 21.4 mmol, 1.6 M in hexanes) in THF (60 mL) at −78° C. was added dropwise over 30 min a solution of 4-bromo-6-fluoro-1-tetrahydropyran-2-yl-indazole (4.00 g, 13.4 mmol) in THF (20 mL). The reaction was warmed to −40° C. for 5 min, re-cooled to −78° C., and DMF (4.2 mL, 53.5 mmol) was added. The reaction mixture was allowed to warm to RT and stirred for 2 h. The reaction was then quenched with a satd. aq. NH4Cl at 0° C. EtOAc was added and the layers were separated, and the aqueous layer was extracted once with EtOAc. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified by SiO2 chromatography to afford 6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbaldehyde (2.18 g, 66%), as a white solid. MS (ESI) m/z: 249.3 [M+1]+.

後処理

  1. temperaturere-cooled to −78° C.
  2. temperatureto warm to RT
  3. customThe reaction was then quenched with a satd
  4. customat 0° C
  5. additionEtOAc was added
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted once with EtOAc
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified by SiO2 chromatography

出典と根拠

ORDレコード
ord-a766bfe82d184a55bdf92e4580d6861f
出典データセット
uspto-grants-2014_01
特許番号
US08637537B2

反応ノート

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