Potassium tert-butoxide → (S)-2-(trimethylsilyl)ethyl 2-(6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methyl-2-oxoquinolin-1(2H)-yl)ethylcarbamate

HRID 931829Notes

Reaction equation

HRID 931829 reaction equation
[C:1]([O:5][C@@H:6]([C:16]1[C:17]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)=[C:18]2[C:23](=[CH:24][C:25]=1[CH3:26])[NH:22][C:21](=[O:27])[CH:20]=[CH:19]2)[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Br[CH2:42][CH2:43][NH:44][C:45](=[O:53])[O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C@@H:6]([C:16]1[C:17]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)=[C:18]2[C:23](=[CH:24][C:25]=1[CH3:26])[N:22]([CH2:42][CH2:43][NH:44][C:45](=[O:53])[O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[C:21](=[O:27])[CH:20]=[CH:19]2)[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:10])[CH3:11])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxide2×HCID 66633689(S)-6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-oneHCID 866919842-(Trimethylsilyl)ethyl 2-bromoethylcarbamate2×

Product 1

HCID 66631813(S)-2-(trimethylsilyl)ethyl 2-(6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methyl-2-oxoquinolin-1(2H)-yl)ethylcarbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-6-(1-tert-butoxy-2-(tert-butyldimethylsilyloxy)ethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one (0.4061 g, 0.812 mmol) in DMF (8.0 mL) was added potassium tert-butoxide (0.137 g, 1.22 mmol) and the mixture stirred for 30 minutes. A solution of 2-(trimethylsilyl)ethyl 2-bromoethylcarbamate (0.327 g, 1.22 mmol) in DMF (1 mL) was added and the reaction mixture was allowed to slowly warm to room temperature overnight. The reaction mixture was cooled to 0° C., potassium tert-butoxide (0.200 g) was added and the resulting reaction mixture was stirred for 30 minutes. A solution of 2-(trimethylsilyl)ethyl 2-bromoethylcarbamate (0.5 g) in DMF (1 mL) was added and the reaction mixture was warmed to room temperature overnight. Reaction mixture was diluted with ethyl acetate and washed with 5% lithium chloride solution (2×), brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexanes) to give desired product a yellow foam (0.2725 g). Some O-alkylation side-product was also observed.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customthe resulting reaction mixture
  3. stirringwas stirred for 30 minutes
  4. temperaturethe reaction mixture was warmed to room temperature overnight
  5. customReaction mixture
  6. washwashed with 5% lithium chloride solution (2×), brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-98f83e25bf5144ba8cd84f0bdb149a1c
Source dataset
uspto-grants-2016_03
Patent number
US09296758B2

Reaction notes

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