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

HRID 447496Notes

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

Conditions

Temperature: 0 °C

Procedure

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

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

Sources & evidence

ORD record: ord-4921748720fc4674bfdac14307c0643e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481525B2

Reaction notes

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