Potassium Carbonate → (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-yl methyl)-1-(6-methyl-2-pyridinyl)-2-piperidinone

HRID 1829171Notes

Reaction equation

HRID 1829171 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH2:16][CH:17]3[O:21][CH2:20][CH2:19][O:18]3)[CH2:14][NH:13][C:12](=[O:15])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(=O)([O-])[O-].[K+].[K+].Br[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=1>CN1CCCC1=O.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH2:16][CH:17]3[O:21][CH2:20][CH2:19][O:18]3)[CH2:14][N:13]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=3)[C:12](=[O:15])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 792052-Bromo-6-methylpyridineHCID 10882069(5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone

Product 1

HCID 58649121(5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-yl methyl)-1-(6-methyl-2-pyridinyl)-2-piperidinone

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone (WO 9807722) (6.5 g, 19.7 mmol), potassium carbonate (3.05 g, 21.7 mmol), copper (I) iodide (400 mg, 2.1 mmol) and 2-bromo-6-methylpyridine (10.2 g, 60 mmol) in 1-methyl-2-pyrrolidinone (200 ml) was stirred at 140° C. for 24 hours. The cooled mixture was partitioned between ethyl acetate and 10% aqueous ammonia, and the layers separated. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with water, then brine (3×), dried (MgSO4) and evaporated under reduced pressure to give a gum. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 100:0) to afford the title compound as a brown solid, 3.02 g.

Workup

  1. customThe cooled mixture was partitioned between ethyl acetate and 10% aqueous ammonia
  2. customthe layers separated
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe combined organic extracts were washed with water
  5. dry with materialbrine (3×), dried (MgSO4)
  6. customevaporated under reduced pressure
  7. customto give a gum
  8. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 100:0)

Sources & evidence

ORD record
ord-50fe384090094a2e9bd3aa3d42777825
Source dataset
uspto-grants-2006_06
Patent number
US07060836B2

Reaction notes

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