Sesamol → 4-chloro-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one

HRID 2385040Notes

Reaction equation

HRID 2385040 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.[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[C:19](=[O:27])[C:20](=[O:26])[NH:21]2>O1CCCC1>[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[C:19]([OH:27])([C:7]1[C:8]([OH:10])=[CH:9][C:4]3[O:3][CH2:2][O:1][C:5]=3[CH:6]=1)[C:20](=[O:26])[NH:21]2

Participants

5

Reactant 3

HCID 68289SesamolHCID 960474-ChloroisatinHCID 178418918HCID 178418918, compound

Product 1

HCID 666726354-chloro-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-oneYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3-benzodioxol-5-ol (4.86 g, 22.0 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise a solution of isopropyl magnesium chloride (49.6 mmol, 24.8 mL, 2.0 M solution in tetrahydrofuran) over 10 min at 0° C. The reaction mixture was stirred for 30 min upon which time 4-chloroisatin (4.00 g, 22.0 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 2 h and 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 (100 mL), washed with saturated ammonium chloride (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 4-chloro-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one (6.70 g, 95%) as a beige solid: mp 250-253° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.30, (s, 1H), 9.04 (s, 1H), 7.20 (s, 1H), 7.12 (t, J=8.0 Hz, 1H), 6.74 (d, J=8.2 Hz, 1H), 6.70 (d, J=7.7 Hz, 1H), 6.45 (s, 1H), 6.17 (s, 1H), 5.88 (d, J=6.7 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 178.1, 148.6, 147.0, 145.6, 139.6, 130.6, 130.1, 129.6, 122.3, 118.6, 108.9, 108.4, 101.1, 97.4, 75.8; MS (ES−) adz 304.2 (M−17), 302.2 (M−17).

Workup

  1. additionwas added in one portion
  2. customquenched by the addition of 10% aqueous hydrochloric acid (25.0 mL)
  3. concentrationthe mixture was concentrated in vacuo to dryness
  4. additionThe residue was diluted with ethyl acetate (100 mL)
  5. washwashed with saturated ammonium chloride (3×30.0 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo to dryness
  9. customThe residue was triturated with hot diethyl ether

Sources & evidence

ORD record
ord-4f3b8fe7d78d4d7b9d38df48074516fc
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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