2,2,6,6-Tetramethylpiperidine → HCID 18379028, compound

HRID 2298983Notes

Reaction equation

HRID 2298983 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[CH3:16][N:17]1[CH:21]=[CH:20][N:19]=[C:18]1[S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Cl:29][C:30]1[CH:57]=[CH:56][C:33]([C:34]([C:36]2[CH:37]=[C:38]3[C:43](=[CH:44][CH:45]=2)[N:42]([CH3:46])[C:41](=[O:47])[CH:40]=[C:39]3[C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([CH:54]=[CH2:55])[CH:49]=2)=[O:35])=[CH:32][CH:31]=1>C1COCC1.COCCOC>[Cl:29][C:30]1[CH:57]=[CH:56][C:33]([C:34]([OH:35])([C:21]2[N:17]([CH3:16])[C:18]([S:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[N:19][CH:20]=2)[C:36]2[CH:37]=[C:38]3[C:43](=[CH:44][CH:45]=2)[N:42]([CH3:46])[C:41](=[O:47])[CH:40]=[C:39]3[C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([CH:54]=[CH2:55])[CH:49]=2)=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 102417681-Methyl-2-phenylsulfanyl-1H-imidazoleHCID 18379026HCID 18379026, compoundHCID 178418339Butyllithium

Product 1

HCID 18379028HCID 18379028, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-78 °C

Procedure

2,2,6,6-tetramethylpiperdine (4.5 mL, 26.5 mMol) was dissolved in a solution of anhydrous THF (100 mL) and anhydrous 1,2-dimethoxyethane (50 mL) under an atmosphere of dry N2 and the solution was then cooled to −78° C. To this solution was added 2.5 M n-butyllithium in hexanes (9.6 mL, 24.1 mMol) and the mixture was stirred for 20 minutes. To this solution was added 1-methyl-2-phenylthio-1-H-imidazole (4.58 g, 24.1 mMol) and the solution was stirred at −78° C. for 45 minutes. 6-(4-Chloro-benzoyl)-1-methyl-4-(3-vinyl-phenyl)-1H-quinolin-2-one (9.64 g, 24.1 mMol) was then added and the solution was slowly warmed to ambient temperature and stirred overnight. The reaction was quenched with saturated aqueous NH4Cl and the solution was partitioned between water and EtOAc. The aqueous layer was washed 2 more times with EtOAc. The EtOAc extracts were combined and dried over Na2SO4, filtered and concentrated under vacuum to give a yellow oil. The oil was chromatographed on flash silica gel eluting with a gradient from EtOAc/hexanes (1:1) to EtOAc/hexanes (4:1) to give 8.66 g of the titled compound as a foam.

Workup

  1. stirringthe solution was stirred at −78° C. for 45 minutes
  2. temperaturethe solution was slowly warmed to ambient temperature
  3. stirringstirred overnight
  4. customThe reaction was quenched with saturated aqueous NH4Cl
  5. customthe solution was partitioned between water and EtOAc
  6. washThe aqueous layer was washed 2 more times with EtOAc
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customto give a yellow oil
  11. customThe oil was chromatographed on flash silica gel eluting with a gradient from EtOAc/hexanes (1:1) to EtOAc/hexanes (4:1)

Sources & evidence

ORD record
ord-226749704fad4ac2b9648550acde0da6
Source dataset
uspto-grants-2002_12
Patent number
US06495564B1

Reaction notes

Loading…