Hydrochloric Acid → N-Methylisatin

HRID 1625161Notes

Reaction equation

HRID 1625161 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].[H-].[Na+].[CH3:14]I.Cl>CN(C)C=O>[CH3:14][N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 7054IsatinHCID 24758Sodium hydride

Product 1

HCID 16358N-MethylisatinYield 84.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A dimethylformamide (hereinafter referred to as DMF) (500 ml) solution of isatin (14.70 g, 100 mmol, purity 98%; manufactured by SIGMA-ALDRICH) was cooled to 0° C. in an ice bath, and sodium hydride (4.73 g, 118 mmol, 60% in oil; manufactured by Tokyo Chemical Industry Co., Ltd.) was added by portions with a spatula over a period of 10 min. After stirring for 15 min, methyl iodide (7.5 mL, 120 mmol) was added by portions with a Komagome pipette over a period of 10 min. The mixture was stirred at 0° C. for 1 hr and was then poured into 1 L of an aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate, and an ethyl acetate phase was washed twice with water. The ethyl acetate phase was concentrated to obtain 13.6 g of a crude product of N-methylisatin (HPLC assay: 79 area %). The HPLC assay was carried out in the same manner as described above.

Workup

  1. stirringThe mixture was stirred at 0° C. for 1 hr
  2. extractionThe mixture was extracted with ethyl acetate
  3. washan ethyl acetate phase was washed twice with water
  4. concentrationThe ethyl acetate phase was concentrated

Sources & evidence

ORD record
ord-b7614bbe87974a3d8328539df6bcb309
Source dataset
uspto-grants-2014_07
Patent number
US08779162B2

Reaction notes

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