Hydrazine hydrate (1:1) → 1-Benzyl-5-methylindolin-2-one

HRID 2281763Notes

Reaction equation

HRID 2281763 reaction equation
[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[C:11](=O)[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>CS(C)=O>[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[CH2:11][C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 22006201H-Indole-2,3-dione, 5-methyl-1-(phenylmethyl)-

Product 1

HCID 581050281-Benzyl-5-methylindolin-2-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
0 °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. temperaturethe resulting clear red solution was heated at 120° C. for 2 h
  3. temperatureAfter cooling to rt
  4. additionit was poured into a 1 L Erlenmeyer flask
  5. washrinsed with H2O (50 mL) and ice
  6. additionwas added until a total volume about 300 mL
  7. addition2 M HCl (50 mL) was added
  8. extractionthe mixture was extracted with EtOAc (200 mL×2
  9. dry with material100 mL), and the organic layer was dried (Na2SO4)
  10. customRemoval of solvents
  11. customby drying under high vacuum for 2 days

Sources & evidence

ORD record
ord-a216ddd2d8554851aa6813ea8aa88404
Source dataset
uspto-grants-2015_09
Patent number
US09139563B2

Reaction notes

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