Methyl iodide → Ethyl 4-(1,3-dioxoisoindolin-2-yl)-1-methylcyclohexanecarboxylate

HRID 712245Notes

Reaction equation

HRID 712245 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:13]1.[Li+].[CH3:24]C([N-]C(C)C)C.CI>C1COCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:13][CH2:14][C:15]([CH3:24])([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 4082309Ethyl 4-(1,3-dioxoisoindolin-2-yl)cyclohexanecarboxylate

Product 1

HCID 58074352Ethyl 4-(1,3-dioxoisoindolin-2-yl)-1-methylcyclohexanecarboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 4-(1,3-dioxoisoindolin-2-yl)cyclohexanecarboxylate (0.30 g, 1.00 mmol) in THF (10 mL) was cooled to −78° C. followed by dropwise addition of LDA (1.60 M in THF, 1.88 mL, 3.00 mmol) at −78° C. The mixture was stirred at the same temperature for 30 minutes followed by addition of MeI (0.311 mL, 5.00 mmol) at −78° C. The temperature of the reaction was slowly raised up to rt and left to stir overnight. The reaction was then cooled to 0° C. and quenched by dropwise addition of saturated NH4Cl solution (30 mL), extracted with EtOAc (3×50 mL) and the combined organics washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the desired product as a viscous liquid (0.30 g, 97%). MS: 316.12 [M+H]+.

Workup

  1. waitleft
  2. stirringto stir overnight
  3. temperatureThe reaction was then cooled to 0° C.
  4. customquenched by dropwise addition of saturated NH4Cl solution (30 mL)
  5. extractionextracted with EtOAc (3×50 mL)
  6. washthe combined organics washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-811bcec85df24ae28dfcf042259117c8
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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