Dimethylformamide → Ethyl 4-(1,3-dioxoisoindolin-2-yl)-1-(2-oxopropyl)cyclo-hexanecarboxylate

HRID 1944734Notes

Reaction equation

HRID 1944734 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH2:23][CH:24]=[CH2:25])[CH2:11][CH2:10][CH:9]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CN(C=[O:30])C>O.Cl.Cl[Cu].Cl[Pd]Cl>[O:21]=[C:20]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[O:22])[N:12]1[CH:9]1[CH2:8][CH2:7][C:6]([CH2:23][C:24](=[O:30])[CH3:25])([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:10]1

Participants

7

Reactant 2

HCID 6228Dimethylformamide2×HCID 672250981-Allyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-cyclohexanecarboxylic acid ethyl ester2×

Product 1

HCID 67225170Ethyl 4-(1,3-dioxoisoindolin-2-yl)-1-(2-oxopropyl)cyclo-hexanecarboxylateYield 100%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 62652Cuprous chlorideCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Procedure

A mixture of CuCl (147 mg, 1.484 mmol) and PdCl2 (46.1 mg, 0.26 mmol) in DMF (24 ml) and water (4 ml) was stirred under an oxygen (balloon) for 3 hours. A solution of 1-Allyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-cyclohexanecarboxylic acid ethyl ester (Intermediate 73, 362 mg, 1.06 mmol) in DMF (16 ml) was added and the mixture was stirred at room temperature for 66 hr under O2. LCMS shows 100% conversion to product and the reaction mixture was diluted with water and 1M HCl, then extracted with ethyl acetate (×3). The organic layers were washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a yellow oil (410 mg, >100%) which was taken to the next step without further purification. LCMS [M+H]=358.3

Workup

  1. stirringthe mixture was stirred at room temperature for 66 hr under O2
  2. extractionextracted with ethyl acetate (×3)
  3. washThe organic layers were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8de3185c1a0644d3969fb81af0b6c560
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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