Lithium Hexamethyldisilazide → Methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanoate

HRID 1020086Notes

Reaction equation

[Li+].[CH3:2][Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13](=[O:32])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][Si:22]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])=[CH:17][CH:16]=1.Br[C:34]1[C:35](C)=[C:36]2[C:41](=[O:42])[NH:40][C:38](=[O:39])[C:37]2=[CH:43][CH:44]=1>C1COCC1>[O:42]=[C:41]1[C:36]2[C:37](=[CH:43][CH:44]=[CH:34][CH:35]=2)[C:38](=[O:39])[N:40]1[CH2:2][CH:14]([C:15]1[CH:20]=[CH:19][C:18]([O:21][Si:22]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:29]([CH3:31])[CH3:30])=[CH:17][CH:16]=1)[C:13]([O:12][CH3:11])=[O:32]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of LiHMDS in THF cooled to −78° C. was added a cooled solution (approx −78° C.) of methyl-2-(4-(triisopropylsilyloxy)phenyl)acetate (E2) in THF via syringe. The solution was stirred at −78° C. for 30 min. Bromo-methyl phthalimide was added directly to the anion, and the solution was immediately removed from the −78° C. bath and placed in an ice bath and stirred for 2 h. The reaction was then poured into NH4Cl(sat) and extracted with EtOAc. The organics were dried (Na2SO4), filtered, and evaporated. Column chromatography 0-20% EtOAc/Hexanes gave pure methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanoate (E3).

Workup

customthe solution was immediately removed from the −78° C. bath
customplaced in an ice bath
stirringstirred for 2 h
additionThe reaction was then poured into NH4Cl(sat)
extractionextracted with EtOAc
dry with materialThe organics were dried (Na2SO4)
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-d1ed4ef235d1400bbebde7717e660cb5
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716310B2

Reaction notes

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