Hydrochloric Acid → 4-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1-methyl-1,3-dihydro-2H-indol-2-one

HRID 1407499Notes

Reaction equation

HRID 1407499 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([OH:11])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.C([Mg]Cl)(C)C.[Br:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[C:20](=[O:29])[C:21](=[O:28])[N:22]2[CH3:27].Cl>ClCCl>[Br:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[C:20]([OH:29])([C:8]1[C:9]([OH:11])=[CH:10][C:5]3[O:4][CH2:3][CH2:2][O:1][C:6]=3[CH:7]=1)[C:21](=[O:28])[N:22]2[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 91152732,3-Dihydro-1,4-benzodioxin-6-olHCID 284924654-Bromo-1-methyl-1H-indole-2,3-dioneHCID 178418918HCID 178418918, compound

Product 1

HCID 673565624-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1-methyl-1,3-dihydro-2H-indol-2-oneYield 80.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2,3-dihydro-1,4-benzodioxin-6-ol (36.0 g, 230 mmol) in dichloromethane (1000 mL) was added isopropylmagnesium chloride (120 mL, 2.0 M solution in tetrahydrofuran, 240 mmol) at 0° C. The mixture was allowed to stir at 0° C. for 1 h and 4-bromo-1-methyl-1H-indole-2,3-dione (48.0 g, 200 mmol) was added. The reaction mixture was stirred at ambient temperature for 22 h and 5% w/v hydrochloric acid was added at 0° C. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was triturated in methanol and washed with diethyl ether to afford 4-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1-methyl-1,3-dihydro-2H-indol-2-one (63.4 g, 80%): 1H NMR (300 MHz, DMSO-d6) δ 8.80 (s, 1H), 7.21-7.13 (m, 2H), 7.01-6.93 (m, 2H), 6.45 (s, 1H), 6.03 (s, 1H), 4.17-4.10 (m, 4H), 3.08 (s, 3H); MS (ES+) m/z 373.8 (M−17), 375.8 (M−17).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 22 h
  2. additionwas added at 0° C
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was triturated in methanol
  9. washwashed with diethyl ether

Sources & evidence

ORD record
ord-320b49035fe74b90980c3866be337415
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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