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 1948086Notes

Reaction equation

HRID 1948086 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, 3H), 1.76-1.78 (m, 1H), 2.07-2.22 (m, 3H), 2.40 (m, 1H), 2.80-2.42 (m, 1H), 3.21 (s, 3H), 4.15 (q, J=6.9 Hz, 2H), 5.92 (s, 1H), 7.44 (d, J=8.5 Hz, 1H), 7.70 (d, J=8.5 Hz, 1H).

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-37c7f8114dcb477eaeb7097820c47e99
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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