Hydrochloric Acid → 2,4-dihydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrile

HRID 1965344Notes

Reaction equation

HRID 1965344 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C([Mg]Cl)(C)C.[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[C:24]2=[O:33])=[CH:20][CH:19]=1.Cl>O1CCCC1.ClCCCl>[OH:1][C:2]1[CH:9]=[C:8]([OH:10])[C:7]([C:25]2([OH:32])[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]([CH2:22][C:21]3[CH:34]=[CH:35][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[C:24]2=[O:33])=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 20487021-(4-methoxybenzyl)-1H-indole-2,3-dioneHCID 30175202,4-DihydroxybenzonitrileHCID 178418918HCID 178418918, compound

Product 1

HCID 673766482,4-dihydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrileYield 79.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2,4-dihydroxybenzonitrile (4.33 g, 32.1 mmol) in tetrahydrofuran (50 mL) and 1,2-dichloroethane (400 mL) was added isopropylmagnesium chloride (17.7 mL, 2.0 M solution in tetrahydrofuran, 35.4 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and at ambient temperature for 2 h, and 1-(4-methoxybenzyl)-1H-indole-2,3-dione (8.58 g, 32.1 mmol) was added to the reaction mixture. The mixture was stirred at reflux for 18 h, cooled to 0° C. and 5% v/v hydrochloric acid was added. The organic layer was separated and washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford 2,4-dihydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrile (10.30 g, 79%): 1H NMR (300 MHz, DMSO-d6) δ 10.81 (s, 1H), 10.35 (s, 1H), 7.80 (s, 1H), 7.32 (d, J=9.0 Hz, 1H), 7.14-7.08 (m, 1H), 6.88-6.84 (m, 4H), 6.75-6.72 (m, 1H), 6.63 (s, 1H), 6.30 (s, 1H), 4.79 (ABq, 2H), 3.70 (s, 3H); MS (ES+) m/z 384.8 (M−17).

Workup

  1. stirringThe mixture was stirred
  2. temperatureat reflux for 18 h
  3. temperaturecooled to 0° C.
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. washeluted with ethyl acetate/hexanes (1/1)

Sources & evidence

ORD record
ord-043ec83d59ab4626b25ea3510d1dac99
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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