Tributyltin Chloride → 6-fluoro-3-(tributylstannyl)-1H-indazole

HRID 246073

反応式

HRID 246073 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](I)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].C([Mg]Cl)(C)C.[CH2:19]([Sn:23]([CH2:29][CH2:30][CH2:31][CH3:32])([CH2:25][CH2:26][CH2:27][CH3:28])Cl)[CH2:20][CH2:21][CH3:22]>C1COCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn:23]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:19][CH2:20][CH2:21][CH3:22])=[N:7][NH:8]2)=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 15096Tributyltin ChlorideHCID 24758Sodium hydrideHCID 178418918HCID 178418918、化合物2 回HCID 178505447HCID 178505447、化合物

生成物 1

HCID 1784482326-fluoro-3-(tributylstannyl)-1H-indazole収率 47%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 6-fluoro-3-iodo-1H-indazole (8.6 g, 32.8 mmol) in THF (200 mL) at 0° C. was slowly added portionwise sodium hydride (60% in mineral oil, 1.58 g, 39.4 mmol). The reaction mixture was stirred at room temperature for 10 min then cooled to −10° C. and isopropylmagnesium chloride (2.0 M in THF, 19.7 mL, 39.4 mmol) was added. The reaction mixture was stirred at −10° C. for 30 min then additional isopropylmagnesium chloride (2.0 M in THF, 8.2 mL, 16.4 mmol) was added. The reaction mixture was stirred at −10° C. for 30 min then tributylchlorostannane (11.6 mL, 42.7 mmol) was slowly added. Stirring was continued at −10° C. for 20 min then at room temperature for 3 h. The reaction mixture was quenched with saturated aqueous NH4Cl then diluted with water and extracted with EtOAc (2×). The combined organics were washed with brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 10% to 20% EtOAc/heptane (0.5% Et3N) to afford 6.53 g (47%) of 6-fluoro-3-tributylstannanyl-1H-indazole as a light brown viscous oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.65 (dd, J=8.7, 5.3 Hz, 1H), 7.20 (dd, J=9.3, 2.1 Hz, 1H), 6.92 (td, J=9.0, 2.1 Hz, 1H), 1.53-1.67 (m, 6H), 1.28-1.43 (m, 6H), 1.20-1.28 (m, 6H), 0.89 (t, J=7.4 Hz, 9H).

後処理

  1. temperaturethen cooled to −10° C.
  2. stirringThe reaction mixture was stirred at −10° C. for 30 min
  3. stirringThe reaction mixture was stirred at −10° C. for 30 min
  4. stirringStirring
  5. waitwas continued at −10° C. for 20 min
  6. waitat room temperature for 3 h
  7. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  8. additionthen diluted with water
  9. extractionextracted with EtOAc (2×)
  10. washThe combined organics were washed with brine
  11. dry with materialthen dried over MgSO4
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel chromatography with 10% to 20% EtOAc/heptane (0.5% Et3N)

出典と根拠

ORDレコード
ord-c11a3a33a69e4ad88047c247d7be6a65
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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