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

HRID 1478292Notes

Reaction equation

HRID 1478292 reaction equation
Br[C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[CH:15]1([CH:18]=[O:19])[CH2:17][CH2:16]1>C1COCC1>[CH3:8][C:7]1[C:2]([CH:18]([CH:15]2[CH2:17][CH2:16]2)[OH:19])=[N:3][CH:4]=[CH:5][C:6]=1[Cl:9]

Participants

5

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 722128482-Bromo-4-chloro-3-methylpyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 12071707(4-Chloro-3-methyl-2-pyridyl)-cyclopropyl-methanolYield 62.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-bromo-3-methyl-4-chloro-pyridine (10.6 g, 57.1 mmol) in freshly distilled THF (120 mL) was cooled down to 0° C. and treated with isopropyl magnesium chloride (45.7 mL, 2.0 M in THF, 91.5 mmol). The resulting mixture was stirred at room temperature for 3 h then cooled to −5° C. Cyclopropane carboxaldehyde (6.83 mL, 91.5 mmol) was added. The reaction mixture was stirred at room temperature for 1 h and quenched by adding water (100 mL), and extracted with ethyl acetate (2×150 mL). The organic phase was separated, dried, and concentrated. The residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1) to afford the title compound as a yellow oil (7.01 g, 62%).

Workup

  1. temperaturethen cooled to −5° C
  2. stirringThe reaction mixture was stirred at room temperature for 1 h
  3. customquenched
  4. additionby adding water (100 mL)
  5. extractionextracted with ethyl acetate (2×150 mL)
  6. customThe organic phase was separated
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-23e4bdff1f2c4bba95b115662ca79463
Source dataset
uspto-grants-2016_08
Patent number
US09403818B2

Reaction notes

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