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

HRID 475312노트

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HRID 475312 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-40 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-a766bfe82d184a55bdf92e4580d6861f
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637537B2

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