Potassium Iodide → 1'-[(2S)-1,4-dioxan-2-ylmethyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 1407748Notes

Reaction equation

HRID 1407748 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].CC1C=CC(S(O[CH2:41][C@H:42]2[CH2:47][O:46][CH2:45][CH2:44][O:43]2)(=O)=O)=CC=1>CN(C)C=O>[O:43]1[CH2:44][CH2:45][O:46][CH2:47][C@@H:42]1[CH2:41][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneHCID 59253203(R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 593523291'-[(2S)-1,4-dioxan-2-ylmethyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneYield 93.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.30 g, 1.07 mmol) and cesium carbonate (0.56 g, 1.71 mmol) in N,N-dimethylformamide (7 mL) was stirred at ambient temperature under nitrogen for 40 min. To this mixture was added potassium iodide (0.05 g, 0.28 mmol) and (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate (0.38 g, 1.40 mmol). The reaction was warmed to 60° C. and stirred for 2 h. The solvent was removed under reduced pressure, and the residue was suspended in ethyl acetate and filtered through Celite. The filtrate was concentrated under reduced pressure and the product was purified by flash column chromatography with dichloromethane/t-butyl methyl ether (19:1) to afford 1′-[(2S)-1,4-dioxan-2-ylmethyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.38 g, 93%) as a colorless solid: mp 147-149° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) (diastereomers) δ7.34-7.28 (m, 1H), 7.17 (d, J=7.2 Hz, 1H), 7.09-7.02 (m, 2H), 6.51 (s, 1H), 6.16, 6.12 (s, 1H), 5.89-5.86 (m, 2H), 4.81, 4.80 (2ABq, 2H), 3.99-3.55 (m, 8H), 3.46-3.38 (m, 1H); 13C NMR (75 MHz, CDCl3) (diastereomers) δ178.0, 177.9, 156.0, 155.9, 149.01, 148.98, 142.7, 142.6, 142.5, 142.4, 132.3, 132.2, 129.02, 128.97, 123.94, 123.87, 123.6, 119.7, 119.5, 109.6, 109.4, 103.14, 103.07, 101.64, 101.62, 93.74, 93.72, 80.5, 80.4, 73.3, 73.2, 69.4, 69.2, 66.8, 66.7, 66.53, 66.49, 58.3, 58.2, 41.9, 41.7; MS (ES+) m/z 381.9 (M+1).

Workup

  1. temperatureThe reaction was warmed to 60° C.
  2. stirringstirred for 2 h
  3. customThe solvent was removed under reduced pressure
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe product was purified by flash column chromatography with dichloromethane/t-butyl methyl ether (19:1)

Sources & evidence

ORD record
ord-fb7f0883a8e4427780518465a56ceaff
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

Loading…