Hydrochloric Acid → 6-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3-dihydro-6H-[1,4]dioxino[2,3-f]indole-7,8-dione

HRID 1965278Notes

Reaction equation

HRID 1965278 reaction equation
[O:1]1[C:6]2=[CH:7][C:8]3[C:9](=[O:15])[C:10](=[O:14])[NH:11][C:12]=3[CH:13]=[C:5]2[O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:33][C@H:34]2[CH2:38][CH2:37][CH2:36][O:35]2)(=O)=O)=CC=1.[I-].[K+].Cl>CN(C)C=O>[O:35]1[CH2:36][CH2:37][CH2:38][C@@H:34]1[CH2:33][N:11]1[C:12]2[CH:13]=[C:5]3[O:4][CH2:3][CH2:2][O:1][C:6]3=[CH:7][C:8]=2[C:9](=[O:15])[C:10]1=[O:14]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 20298022,3-dihydro-6H-[1,4]dioxino[2,3-f]indole-7,8-dioneHCID 7033050(R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 685985166-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3-dihydro-6H-[1,4]dioxino[2,3-f]indole-7,8-dioneYield 20.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2H-[1,4]dioxino[2,3-f]indole-7,8(3H,6H)-dione (2.05 g, 10.0 mmol) in dry N,N-dimethylformamide (100 mL) was added cesium carbonate (4.4 g, 12.0 mmol) at ambient temperature. The dark mixture was stirred for 1 h, followed by the addition of (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate (3.07 g, 12.0 mmol) in one portion and potassium iodide (0.66 g, 4.0 mmol). The dark mixture was stirred at 70° C. for 16 h. The mixture was poured into 5% hydrochloric acid solution (300 mL) and extracted with ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography with ethyl acetate in hexanes (30 to 50% gradient) to afford 6-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3-dihydro-6H-[1,4]dioxino[2,3-f]indole-7,8-dione (0.59 g, 20%): MS (ES+) m/z 290.2 (M+1).

Workup

  1. stirringThe dark mixture was stirred at 70° C. for 16 h
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography with ethyl acetate in hexanes (30 to 50% gradient)

Sources & evidence

ORD record
ord-6d155dd4a4c64b92b7b7e4fff80a4582
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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