Benzyl Bromide → 1H-Indole-2,3-dione, 5-methyl-1-(phenylmethyl)-

HRID 2383629Notes

Reaction equation

HRID 2383629 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].C([O-])([O-])=O.[K+].[K+].[CH:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[CH:21][CH:20]=1>CN(C=O)C>[CH2:25]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=2)[C:5](=[O:12])[C:6]1=[O:11])[C:22]1[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 118405-Methylisatin

Product 1

HCID 22006201H-Indole-2,3-dione, 5-methyl-1-(phenylmethyl)-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 5-methylisatin (8.05 g, 50 mmol) and K2CO3 (8.16 g, 60 mmol) in DMF (100 mL) was added BnBr (6.5 mL, 55 mmol) dropwise over 2 min. After addition, the resulting mixture was heated in an oil bath at 75° C. for 1.5 h. After cooling to rt, the reaction mixture was poured onto ice/cold water (250 mL), rinsed with H2O (50 mL) and stirred for 5 min. The resulting precipitates were collected by suction filtration and air dried to give 1-benzyl-5-methylisatin as dark red solid. MS ESI 252.0 [M+H]+, calcd for [C16H13NO2+H]+ 252.1. 1-Benzyl-5-methylisatin was suspended in DMSO (100 mL) and cooled to 0° C. Hydrazine hydrate (5 mL) was added dropwise over 5 min. After addition, the resulting clear red solution was heated at 120° C. for 2 h then 140° C. for 5 h. After cooling to rt, it was poured into a 1 L Erlenmeyer flask, rinsed with H2O (50 mL) and ice was added until a total volume about 300 mL. 2 M HCl (50 mL) was added and the mixture was extracted with EtOAc (200 mL×2, then 100 mL), and the organic layer was dried (Na2SO4). Removal of solvents followed by drying under high vacuum for 2 days gave the title compound as a dark red solid (12.53 g, quantitative yield over 2 steps, contained some DMSO residue). 1H NMR (400 MHz, CDCl3) δ 7.35-7.29 (m, 5H), 7.09 (s, 1H), 6.97 (d, J=7.6 Hz, 1H), 6.61 (d, J=8.0 Hz, 1H), 4.91 (s, 2H), 3.60 (s, 2H), 2.31 (s, 3H); MS ESI 238.0 [M+H]+, calcd for [C16H15NO+H]+ 238.1.

Workup

  1. additionAfter addition
  2. temperatureAfter cooling to rt
  3. additionthe reaction mixture was poured onto ice/cold water (250 mL)
  4. washrinsed with H2O (50 mL)
  5. customThe resulting precipitates
  6. filtrationwere collected by suction filtration and air
  7. customdried

Sources & evidence

ORD record
ord-59a46a4db7f744b09d7395102ec34c90
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

Loading…