Lithium Hexamethyldisilazide → Methyl 2-(5-((tert-butyldimethylsilyloxy)methyl)thiophen-2-yl)-3-(1,3-dioxoisoindolin-2-yl)propanoate

HRID 1020117Notes

Reaction equation

[Li+].[CH3:2][Si]([N-][Si](C)(C)C)(C)C.[Si:11]([O:18][CH2:19][C:20]1[S:24][C:23]([CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].Br[C:31]1[C:32](C)=[C:33]2[C:38](=[O:39])[NH:37][C:35](=[O:36])[C:34]2=[CH:40][CH:41]=1>C1COCC1>[Si:11]([O:18][CH2:19][C:20]1[S:24][C:23]([CH:25]([CH2:2][N:37]2[C:38](=[O:39])[C:33]3[C:34](=[CH:40][CH:41]=[CH:31][CH:32]=3)[C:35]2=[O:36])[C:26]([O:28][CH3:29])=[O:27])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:12])[CH3:13]

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-(5-((tert-butyldimethylsilyloxy)methyl)thiophen-2-yl)acetate (E232) in THF via syringe. The solution was stirred at −78° C. for 30 min. Bromo-methylphthalimide 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 (SiO2, 15-20% EtOAc/Hexanes) gave pure methyl 2-(5-((tert-butyldimethylsilyloxy)methyl)thiophen-2-yl)-3-(1,3-dioxoisoindolin-2-yl)propanoate (E233).

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-ab9f89f97703436e8f205594041e849d
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716310B2

Reaction notes

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