Sodium hydride → 4-Chloro-2-(1-cyclopropyl-2-methoxyvinyl)-3-methylpyridine

HRID 1478294Notes

Reaction equation

HRID 1478294 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].[CH3:26][C:27]1[C:28]([C:34]([CH:36]2[CH2:38][CH2:37]2)=O)=[N:29][CH:30]=[CH:31][C:32]=1[Cl:33]>C1COCC1>[CH:36]1([C:34]([C:28]2[C:27]([CH3:26])=[C:32]([Cl:33])[CH:31]=[CH:30][N:29]=2)=[CH:2][O:3][CH3:4])[CH2:38][CH2:37]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 66980317(4-Chloro-3-methyl-2-pyridyl)cyclopropylketone

Product 1

HCID 669802244-Chloro-2-(1-cyclopropyl-2-methoxyvinyl)-3-methylpyridineYield 82.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

A solution of methoxymethyl triphenylphosphonium chloride (17.9 g, 52.3 mmol) in dry THF (80 mL) was treated with NaH (2.79 g, 69.8 mmol) at 0° C. for 3 h. To this mixture was added a solution of (3-methyl-4-chloro-pyridin-2-yl)-cyclopropyl-methanone (6.82 g, 34.9 mmol) in dry THF (20 mL). The reaction mixture was heated at 40° C. overnight. The reaction mixture was cooled down to room temperature and filtered. The filtrate was concentrated to dryness. The residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1) to afford the title compound (6.41 g, 82%).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated to dryness
  4. customThe residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-70627d9de87643d5a0523125e04d7cad
Source dataset
uspto-grants-2016_08
Patent number
US09403818B2

Reaction notes

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