Cesium carbonate → Ethyl 1-methyl-4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-ene-1-carboxylate

HRID 511517Notes

Reaction equation

HRID 511517 reaction equation
O1CCOCC1.[CH3:7][N:8]1[CH2:16][C:15]2[C:10](=[C:11]([N+:26]([O-:28])=[O:27])[CH:12]=[CH:13][C:14]=2B2OC(C)(C)C(C)(C)O2)[C:9]1=[O:29].[CH3:30][C:31]1([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:36][CH2:35][C:34](OS(C(F)(F)F)(=O)=O)=[CH:33][CH2:32]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:30][C:31]1([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:36][CH2:35][C:34]([C:14]2[CH:13]=[CH:12][C:11]([N+:26]([O-:28])=[O:27])=[C:10]3[C:15]=2[CH2:16][N:8]([CH3:7])[C:9]3=[O:29])=[CH:33][CH2:32]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 672539682-Methyl-7-nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-oneHCID 86654053Ethyl 1-methyl-4-(trifluoromethylsulfonyloxy)cyclohex-3-enecarboxylate2×

Product 1

HCID 67254909Ethyl 1-methyl-4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-ene-1-carboxylateYield 84.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of dioxane and water (15 mL, 4:1) was degassed for 30 min. 2-Methyl-7-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindol-1-one (373 mg, 1.19 mmol), ethyl 1-methyl-4-{[(trifluoromethyl)sulfonyl]oxy}cyclohex-3-ene-1-carboxylate (Compound 282E, 300 mg, 0.92 mmol), Pd (PPh3)4 (106 mg, 0.092 mmol), and cesium carbonate (747 mg, 2.3 mmol) were then added. The reaction mixture was heated at 70° C. for 2 h. After cooled to room temperature, the mixture was filtered and concentrated to dryness, the residue was purified by column chromatography (SiO2, 5% ethyl acetate/dichloromethane) to give 278 mg (yield: 77%) of the desired compound. 1H NMR (CDCl3, 300 MHz): δ=1.26 (t, J=6.9 Hz, 3 H), 1.76-1.78 (m, 1 H), 2.07-2.22 (m, 3 H), 2.40 (m, 1 H), 2.80-2.42 (m, 1 H), 3.21 (s, 3 H), 4.15 (q, J=6.9 Hz, 2 H), 5.92 (s, 1 H), 7.44 (d, J=8.5 Hz, 1 H), 7.70 (d, J=8.5 Hz, 1 H).

Workup

  1. customwas degassed for 30 min
  2. temperatureAfter cooled to room temperature
  3. filtrationthe mixture was filtered
  4. concentrationconcentrated to dryness
  5. customthe residue was purified by column chromatography (SiO2, 5% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-e89eb75f889f49d7ac230f49865f509f
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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