5-Bromo-2-fluorobenzaldehyde → 2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine

HRID 335955ノート

反応式

HRID 335955 の反応式
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([F:14])[C:3]=1[O:15][CH2:16][O:17][CH3:18].C([Li])CCC.BrC1C=CC(F)=C(C=1)C=O>O1CCCC1>[F:14][C:4]1[C:3]([O:15][CH2:16][O:17][CH3:18])=[CH:2][CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[N:5]=1

参加物

5

反応物 3

HCID 7363275-Bromo-2-fluorobenzaldehydeHCID 673828784-Bromo-2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridineHCID 178418339Butyllithium

生成物 1

HCID 673830702-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine収率 12.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

4-Bromo-2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine (1.62 g, 5.06 mmol) was dissolved in dry tetrahydrofuran (50 mL) under nitrogen and cooled in a dry ice bath. Butyllithium solution (2.5 M in hexanes, 2.2 mL, 5.50 mmol) was added and the reaction stirred for 5 min. A solution of 5-bromo-2-fluorobenzaldehyde (1.03 g, 5.06 mmol) in dry THF (10 mL) was added and the reaction stirred for 35 min then quenched by addition of saturated ammonium chloride (20 mL). Water (100 mL) and EtOAc (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to EtOAc gradient) gave recovered starting material (0.30 g, 18%), debrominated 2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridine (0.15 g, 0.61 mmol, 12.0% yield) and the desired (5-bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)methanol (0.85 g, 1.90 mmol)

後処理

  1. temperaturecooled in a dry ice bath
  2. stirringthe reaction stirred for 35 min
  3. customthen quenched by addition of saturated ammonium chloride (20 mL)
  4. additionWater (100 mL) and EtOAc (100 mL) were added
  5. additionthe phases mixed
  6. customseparated
  7. dry with materialThe organic was dried with magnesium sulfate
  8. customevaporated to dryness under reduced pressure
  9. customPurification
  10. customgave
  11. customrecovered

出典と根拠

ORDレコード
ord-89505d091e214be59aeacf602664c79f
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

反応ノート

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