Water → (4-Chloro-3-methyl-2-pyridyl)-cyclopropyl-methanol

HRID 1478298Notes

Reaction equation

HRID 1478298 reaction equation
Br[C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=[CH:4][N:3]=1.[CH:10]1([CH:13]=[O:14])[CH2:12][CH2:11]1.O>C1COCC1>[Cl:9][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH:13]([CH:10]2[CH2:12][CH2:11]2)[OH:14])[C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 962WaterHCID 123114CyclopropanecarboxaldehydeHCID 722128482-Bromo-4-chloro-3-methylpyridine

Product 1

HCID 12071707(4-Chloro-3-methyl-2-pyridyl)-cyclopropyl-methanolYield 62.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-bromo-4-chloro-3-methylpyridine (7 g, 28.1 mmol) in dry THF (150 mL) was cooled down to 0° C. An isopropyl magnesium chloride-Lithium chloride complex (26 mL, 33.8 mmol) was added carefully so temperature would not rise above 5° C. during the addition. The mixture was allowed to warm up to room temperature and was stirred for 1 h. The reaction mixture was cooled down to 0° C. and cyclopropane carboxaldehyde (2.5 mL, 33.5 mmol) was added carefully so temperature would not rise above 5° C. during the addition. The mixture was allowed to warm up to room temperature and was stirred for 1 h. The reaction mixture was cooled to 0° C. and water (150 mL) was added carefully so temperature would not rise above 10° C. during the addition. The mixture was allowed to warm up to room temperature and was stirred for 1 h. The mixture was extracted with ethyl acetate (3×100 mL). The combined organic phases were washed with brine (100 mL), dried over sodium sulfate and evaporated. The residue was purified by flash chromatography over silica gel (0-30% ethyl acetate in heptane) yielding a yellow oil (3.47 g, 16.8%).

Workup

  1. additionAn isopropyl magnesium chloride-Lithium chloride complex (26 mL, 33.8 mmol) was added carefully so temperature would not
  2. additionrise above 5° C. during the addition
  3. temperatureThe reaction mixture was cooled down to 0° C.
  4. additionrise above 5° C. during the addition
  5. temperatureto warm up to room temperature
  6. stirringwas stirred for 1 h
  7. temperatureThe reaction mixture was cooled to 0° C.
  8. additionrise above 10° C. during the addition
  9. temperatureto warm up to room temperature
  10. stirringwas stirred for 1 h
  11. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
  12. washThe combined organic phases were washed with brine (100 mL)
  13. dry with materialdried over sodium sulfate
  14. customevaporated
  15. customThe residue was purified by flash chromatography over silica gel (0-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b44e35e8c9814c059fcc8b01ff374dfc
Source dataset
uspto-grants-2016_08
Patent number
US09403818B2

Reaction notes

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