Imidazole → (S)-6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one

HRID 931828Notes

Reaction equation

HRID 931828 reaction equation
[C:1]([O:5][C@@H:6]([C:9]1[C:10]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[C:11]2[C:16](=[CH:17][C:18]=1[CH3:19])[NH:15][C:14](=[O:20])[CH:13]=[CH:12]2)[CH2:7][OH:8])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:33](Cl)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C@@H:6]([C:9]1[C:10]([C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)=[C:11]2[C:16](=[CH:17][C:18]=1[CH3:19])[NH:15][C:14](=[O:20])[CH:13]=[CH:12]2)[CH2:7][O:8][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 66633284(S)-6-(1-tert-butoxy-2-hydroxyethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one

Product 1

HCID 66633689(S)-6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-oneYield 74.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-6-(1-tert-butoxy-2-hydroxyethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one (8K) (0.5175 g, 1.34 mmol) in DMF (5.0 mL), was added imidazole (0.204 g, 4.02 mmol), followed by tert-butyldimethylsilyl chloride (0.243 g, 1.61 mmol) at 0° C. The reaction mixture was warmed to room temperature overnight. Additional imidazole (0.2 g) and tert-butyldimethylsilyl chloride (0.30 g) were added and the mixture stirred for another 2 hours. The reaction mixture was the diluted with ethyl acetate, washed with 5% lithium chloride solution (2×), brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 20 to 60% ethyl acetate/hexanes) to give a yellow foam (0.500 g). LCMS-ESI+ (m/z): calcd for C28H39ClNO3Si: 501.1;

Workup

  1. washwashed with 5% lithium chloride solution (2×), brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 20 to 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-246d1e5694b042a8bef83dcffc1e18ba
Source dataset
uspto-grants-2016_03
Patent number
US09296758B2

Reaction notes

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