1H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)- → Methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(thiophen-3-yl)propanoate

HRID 509231Notes

Reaction equation

HRID 509231 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][C:7]([O:9][CH3:10])=[O:8])=[CH:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:22][N:23]1[C:27](=[O:28])[C:26]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]2[C:24]1=[O:33].C([O-])(O)=O.[Na+]>C1COCC1>[O:33]=[C:24]1[C:25]2[C:26](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27](=[O:28])[N:23]1[CH2:22][CH:6]([C:3]1[CH:4]=[CH:5][S:1][CH:2]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 4

HCID 792441H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)-HCID 94041Methyl 3-thienylacetateHCID 516892Sodium BicarbonateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 59161752Methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(thiophen-3-yl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To pure methyl 2-(thiophen-3-yl)acetate (E41) in THF cooled to −78° C. was added LiHMDS, and the solution stirred at −78° C. for 30 min. Then N-(bromomethyl)phthalimide was added directly, and the solution was allowed to warm to 0° C. The mixture was poured into NaHCO3 (sat), extracted with EtOAc, dried (Na2SO4), filtered, and evaporated. Column chromatography (SiO2, 0-40% EtOAc/Hex) gave pure methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(thiophen-3-yl)propanoate (E45).

Workup

  1. temperatureto warm to 0° C
  2. extractionextracted with EtOAc
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-6734d85abea24a72aefaa20fef2dac69
Source dataset
uspto-grants-2015_08
Patent number
US09096569B2

Reaction notes

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