Triethylamine → 4-bromo-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1-(pyridin-2-ylmethyl)-1,3-dihydro-2H-indol-2-one

HRID 1259632Notes

Reaction equation

HRID 1259632 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](O)([C:19]1[C:20]([OH:28])=[CH:21][C:22]3[O:26][CH2:25][CH2:24][C:23]=3[CH:27]=1)[C:5](=[O:18])[N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1.C(N(CC)CC)C.O=S(Cl)Cl>ClCCl.C(O)(=O)C.O1CCCC1.[Zn]>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([C:19]1[C:20]([OH:28])=[CH:21][C:22]3[O:26][CH2:25][CH2:24][C:23]=3[CH:27]=1)[C:5](=[O:18])[N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 588725084-bromo-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1-(pyridin-2-ylmethyl)-1,3-dihydro-2H-indol-2-one

Product 1

HCID 588724584-bromo-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1-(pyridin-2-ylmethyl)-1,3-dihydro-2H-indol-2-oneYield 138.3%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6344DichloromethaneSolventHCID 23444217Acetic acid tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-bromo-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1-(pyridin-2-ylmethyl)-1,3-dihydro-2H-indol-2-one (1.12 g, 2.48 mmol) in anhydrous dichloromethane (25.0 mL) was added triethylamine (1.40 mL, 9.91 mmol) and SOCl2 (0.40 mL, 4.96 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 2 h and quenched with water (30.0 mL). The organic layer was separated, washed with water (3×30.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness to give a gummy material. The residue was dissolved in acetic acid/tetrahydrofuran (3.00 mL/22.0 mL) followed by the addition of zinc dust (0.81 g, 12.4 mmol) in one portion. The reaction mixture was stirred at ambient temperature for 16 h. After the solid was filtered, the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with water (3×30.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness to give the title compound (1.50 g, 77%) as a gummy material: MS (ES+) m/z 437.3 (M+1).

Workup

  1. customquenched with water (30.0 mL)
  2. customThe organic layer was separated
  3. washwashed with water (3×30.0 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. customto give a gummy material
  8. stirringThe reaction mixture was stirred at ambient temperature for 16 h
  9. filtrationAfter the solid was filtered
  10. customthe solvent was removed in vacuo
  11. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  12. washwashed with water (3×30.0 mL)
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-770900f982184fad9c3e67310232eae1
Source dataset
uspto-grants-2013_06
Patent number
US08466188B2

Reaction notes

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