Sesamol → 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one

HRID 2385044Notes

Reaction equation

HRID 2385044 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([OH:10])=[CH:9][C:4]=2[O:3][CH2:2]1.C([Mg]Cl)(C)C.[F:16][C:17]([F:30])([F:29])[C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:26]=1[NH:25][C:24](=[O:27])[C:23]2=[O:28]>O1CCCC1>[OH:28][C:23]1([C:7]2[C:8]([OH:10])=[CH:9][C:4]3[O:3][CH2:2][O:1][C:5]=3[CH:6]=2)[C:22]2[C:26](=[C:18]([C:17]([F:16])([F:29])[F:30])[CH:19]=[CH:20][CH:21]=2)[NH:25][C:24]1=[O:27]

Participants

5

Reactant 3

HCID 68289SesamolHCID 6045757-TrifluoromethylisatinHCID 178418918HCID 178418918, compound

Product 1

HCID 673566523-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-oneYield 175%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3-benzodioxol-5-ol (9.63 g, 69.7 mmol) in anhydrous tetrahydrofuran (200 mL) was added dropwise a solution of isopropyl magnesium chloride (92.9 mmol, 46.5 mL, 2.0 M solution in tetrahydrofuran) over 30 min at 0° C. 7-Trifluoromethylisatin (4.00 g, 22.0 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 4 h and the reaction was quenched by the addition of 10% aqueous hydrochloric acid (25.0 mL) and the mixture was concentrated in vacuo to dryness. The residue was diluted with ethyl acetate (200 mL), washed with saturated ammonium chloride (3×30.0 mL), brine (3×30.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with hot diethyl ether to afford 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (13.6 g, 83%): 1H NMR (300 MHz, DMSO-d6) δ 10.65 (s, 1H), 9.21 (s, 1H), 7.38 (d, J=7.8 Hz, 1H), 7.22 (s, 1H), 7.07 (d, J=7.2 Hz, 1H), 6.95 (dd, J=7.7, 7.7 Hz, 1H), 6.57 (s, 1H), 6.17 (s, 1H), 5.89 (d, J=6.2 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 179.2, 148.6, 147.3, 141.0, 139.9, 135.7, 127.9, 125.3, 124.3, 121.7, 119.8, 110.1, 107.2, 101.2, 97.7, 73.9; MS (ES−) m/z 352.2 (M−1).

Workup

  1. customthe reaction was quenched by the addition of 10% aqueous hydrochloric acid (25.0 mL)
  2. concentrationthe mixture was concentrated in vacuo to dryness
  3. additionThe residue was diluted with ethyl acetate (200 mL)
  4. washwashed with saturated ammonium chloride (3×30.0 mL), brine (3×30.0 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo to dryness
  8. customThe residue was triturated with hot diethyl ether

Sources & evidence

ORD record
ord-3eaf94b80ea84ac69624ec0362f3409c
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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