Benzyl 3-hydroxyphenyl ether → [4-(benzyloxy)-2-hydroxyphenyl]-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one

HRID 1965303Notes

Reaction equation

HRID 1965303 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[C:21]1([CH:27]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30](=[O:37])[C:29]2=[O:38])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1.ClCCl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:30]2([OH:37])[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:28]([CH:27]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:29]2=[O:38])=[C:11]([OH:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 138048Benzyl 3-hydroxyphenyl etherHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 178418918HCID 178418918, compound

Product 1

HCID 66672327[4-(benzyloxy)-2-hydroxyphenyl]-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-oneYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-(benzyloxy)phenol (8.7 g, 43.5 mmol) in tetrahydrofuran (100 mL) was added isopropylmagnesium chloride (22.7 mL, 2 M tetrahydrofuran solution, 45.4 mmol) slowly at 0° C. The mixture was allowed to stir for 30 min at 0° C., and concentrated in vacuo to dryness. Dichloromethane (100 mL) was added, followed by the addition of a solution of 1-(diphenylmethyl)-1H-indole-2,3-dione (12.4 g, 39.5 mmol) in dichloromethane (50 mL) at 0° C. The mixture was stirred at room temperature for 16 h, and quenched with saturated ammonium chloride solution. The organic layer was washed with water, dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The obtained solid was recrystallized from ethyl acetate/hexanes to afford 3-[4-(benzyloxy)-2-hydroxyphenyl]-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one (19.60 g, 97%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.49-7.43 (m, 1H), 7.42-7.25 (m, 13H), 7.23-7.17 (m, 2H), 7.12-7.04 (m, 2H), 6.91 (s, 1H), 6.72-6.62 (m, 2H), 6.51-6.44 (m, 1H), 6.39 (dd, J=8.6, 2.4 Hz, 1H), 4.99 (s, 2H); MS (ES+) m/z 536.3 (M+23).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. additionDichloromethane (100 mL) was added
  3. stirringThe mixture was stirred at room temperature for 16 h
  4. customquenched with saturated ammonium chloride solution
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo to dryness
  9. customThe obtained solid was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8fc27210fc2646469e241295b114fe4b
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

Loading…