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

HRID 1407426Notes

Reaction equation

HRID 1407426 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-49e6729868294bff99b6b0cd8cc4a164
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

Loading…