Sodium hydride → 4-bromo-1-(Pyridin-2-ylmethyl)-1H-indole-2,3-dione

HRID 645079Notes

Reaction equation

HRID 645079 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[C:5](=[O:11])[NH:6]2.[H-].[Na+].Br.Br[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1>CN(C)C=O>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:12])[C:5](=[O:11])[N:6]2[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 45000124-Bromoisatin

Product 1

HCID 284924914-bromo-1-(Pyridin-2-ylmethyl)-1H-indole-2,3-dioneYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-bromoisatin (8.94 g, 39.5 mmol) in anhydrous N,N-dimethylformamide (100 mL) was added sodium hydride (3.34 g, 86.9 mmol, 60% dispersion in mineral oil) in portions at 0° C. The brown reaction mixture was stirred for 30 min followed by the addition of a solution of 2-(bromomethyl)pyridine hydrobromide (10.0 g, 39.5 mmol) neutralized with sodium hydride (1.52 g, 39.5 mmol, 60% dispersion in mineral oil) in N,N-dimethylformamide at 0° C. The reaction mixture was stirred for 16 h and quenched with water (100 mL). The reaction mixture was extracted with diethyl ether (3×100 mL) and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers was washed with water (5×200 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with ether to afford the title compound (10.6 g, 85%) as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 8.53 (d, 1H), 7.67 (t, 1H), 7.30 (t, 2H), 7.25-7.19 (m, 2H), 6.94 (d, 1H), 5.04 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ 180.5, 157.3, 154.2, 152.3, 149.5, 138.4, 137.5, 128.6, 123.3, 122.3, 121.5, 116.4, 110.3, 45.8.

Workup

  1. stirringThe reaction mixture was stirred for 16 h
  2. customquenched with water (100 mL)
  3. extractionThe reaction mixture was extracted with diethyl ether (3×100 mL)
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  5. washThe combined organic layers was washed with water (5×200 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 ether

Sources & evidence

ORD record
ord-995990e0606542e5a128107b48471d03
Source dataset
uspto-grants-2010_04
Patent number
US07700641B2

Reaction notes

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