2-Fluoropyridine → (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-1-(2-pyridinyl)-2-piperidinone

HRID 1829170Notes

Reaction equation

HRID 1829170 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:9]=[C:10]([C@:15]2([CH2:22][CH:23]3[O:27][CH2:26][CH2:25][O:24]3)[CH2:20][NH:19][C:18](=[O:21])[CH2:17][CH2:16]2)[CH:11]=[CH:12][C:13]=1[Cl:14].F[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1>COCCOC>[Cl:7][C:8]1[CH:9]=[C:10]([C@:15]2([CH2:22][CH:23]3[O:27][CH2:26][CH2:25][O:24]3)[CH2:20][N:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:18](=[O:21])[CH2:17][CH2:16]2)[CH:11]=[CH:12][C:13]=1[Cl:14]

Participants

5

Reactant 3

HCID 97462-Fluoropyridine2×HCID 10882069(5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinoneHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 58649167(5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-1-(2-pyridinyl)-2-piperidinone

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Potassium tert-butoxide (68 g, 0.606 mol) was added to a suspension of (5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone (WO 9807722) (200 g, 0.606 mol) in 1,2-dimethoxyethane (700 ml), and the mixture heated under reflux for 1 hour. 2-Fluoropyridine (59 g, 0.606 mol) was then added and the mixture stirred under reflux for 1 hour. Additional potassium tert-butoxide (34 g, 0.303 mol) and 2-fluoropyridine (30 g, 0.303 mol) were added and the reaction mixture stirred under reflux for a further hour. The cooled mixture was partitioned with water (500 ml), and the aqueous layer then extracted with ethyl acetate (2×500 ml). The combined organic extracts were dried (MgSO4), and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (20:80 to 100:0) to afford the title compound as a clear gum, 129 g.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 1 hour
  3. temperatureunder reflux for 1 hour
  4. stirringthe reaction mixture stirred
  5. temperatureunder reflux for a further hour
  6. customThe cooled mixture was partitioned with water (500 ml)
  7. extractionthe aqueous layer then extracted with ethyl acetate (2×500 ml)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. customevaporated under reduced pressure
  10. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (20:80 to 100:0)

Sources & evidence

ORD record
ord-7709fe715a8646a68a9b4b4dec1e2a4b
Source dataset
uspto-grants-2006_06
Patent number
US07060836B2

Reaction notes

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