Sulfuric Acid → 2-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-acetaldehyde

HRID 1854822Notes

Reaction equation

HRID 1854822 reaction equation
[CH:1]1([C:4]([C:8]2[C:13]([CH3:14])=[C:12]([Cl:15])[CH:11]=[CH:10][N:9]=2)=[CH:5][O:6]C)[CH2:3][CH2:2]1.S(=O)(=O)(O)O.[OH-].[Na+]>C(O)(=O)C>[CH3:14][C:13]1[C:8]([CH:4]([CH:1]2[CH2:3][CH2:2]2)[CH:5]=[O:6])=[N:9][CH:10]=[CH:11][C:12]=1[Cl:15]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 669802244-Chloro-2-(1-cyclopropyl-2-methoxyvinyl)-3-methylpyridine

Product 1

HCID 186293552-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-acetaldehydeYield 80.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 2-(1-cyclopropyl-2-methoxy-vinyl)-3-methyl-4-chloro-pyridine (6.41 g, 28.7 mmol) in acetic acid (50 mL) was treated with sulfuric acid (6.52 mL, 143 mmol) at room temperature overnight. The reaction mixture was neutralized with 2N NaOH to pH 8-9 extracted with ethyl acetate (2×100 mL). The organic phases were combined, dried, and concentrated. The residue was purified by flash silica column chromatography (hexane/ethyl acetate=2:1) to afford the title compound as a yellow solid (4.83 g, 80%). ESI-MS m/z: 210 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ ppm: 9.89 (d, J=2.4 Hz, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.26 (d, J=5.4 Hz, 1H), 3.26-3.28 (m, 1H), 2.35 (s, 3H), 1.53-1.59 (m, 1H), 0.55-0.79 (m, 2H), 0.25-0.39 (m, 2H).

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by flash silica column chromatography (hexane/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-1c398f0e624a44fdba58fce0e07a7bac
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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