Methyl vinyl ketone → 4-(3-Chloropyridin-2-yl)-4-methylcyclohex-2-enone

HRID 2197604Notes

Reaction equation

HRID 2197604 reaction equation
[Cl:1][C:2]1[C:3]([CH:8]([CH3:11])[CH:9]=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[OH-].[K+].[CH:14]([C:16]([CH3:18])=[O:17])=[CH2:15]>C(OCC)C>[Cl:1][C:2]1[C:3]([C:8]2([CH3:11])[CH2:15][CH2:14][C:16](=[O:17])[CH:18]=[CH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 14797Potassium HydroxideHCID 866302832-(3-Chloropyridin-2-yl)propanal

Product 1

HCID 674999494-(3-Chloropyridin-2-yl)-4-methylcyclohex-2-enoneYield 22%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a 0° C. solution of the product of Example 38D (0.71 g, 4.19 mmol) in diethyl ether (10 mL) was added a solution of potassium hydroxide (3M in methanol, 0.56 mL, 1.68 mmol), followed by methyl vinyl ketone (0.47 g, 0.55 mL, 6.70 mmol). The reaction was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was diluted with diethyl ether, and washed with water and brine. The organic layer was concentrated, and the residue was chromatographed on silica gel eluting with 25% ethyl acetate-hexane to give the title compound (0.20 g, 22%). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.53 (dd, J=1.5, 4.6, 1H), 7.92 (dd, J=1.5, 8.0, 1H), 7.45-7.26 (m, 2H), 5.92 (d, J=10.2, 1H), 2.82-2.67 (m, 1H), 2.64-2.52 (m, 1H), 2.31 (ddd, J=4.8, 7.2, 17.3, 1H), 2.12-2.00 (m, 1H). MS (DCI) m/z 222 (M+H)+.

Workup

  1. washwashed with water and brine
  2. concentrationThe organic layer was concentrated
  3. customthe residue was chromatographed on silica gel eluting with 25% ethyl acetate-hexane

Sources & evidence

ORD record
ord-79ba0d517b3746b0bd21f75fffc77a6a
Source dataset
uspto-grants-2012_12
Patent number
US08338603B2

Reaction notes

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