Methyl iodide → 1-(4-Acetylaminophenyl)-3-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione
Reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]23[CH2:16][CH:15]2[C:14](=[O:17])[NH:13][C:12]3=[O:18])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[H-].[Na+].[CH3:21]I>CN(C)C=O>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]23[CH2:16][CH:15]2[C:14](=[O:17])[N:13]([CH3:21])[C:12]3=[O:18])=[CH:9][CH:10]=1)(=[O:3])[CH3:2]Participants
Conditions
- Temperature
- 20 °C
Procedure
1.2 g of 1-(4-acetylaminophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione, 120 mg of sodium hydride and 25 ml of N,N'-dimethylformamide are stirred, under nitrogen, for 15 minutes at 50° C. The mixture is cooled to 20° C. and then a solution of 0.32 ml of methyl iodide in 2.5 ml of dimethylformamide is slowly added dropwise. The reaction mixture is stirred for 16 hours at room temperature. Excess sodium hydride is destroyed with methanol and the reaction mixture is freed from solvent in a high vacuum. The residue is partitioned repeatedly between ethyl acetate and a dilute solution of sodium chloride. The organic phases are dried over magnesium sulfate, filtered, concentrated, and the residue is crystallised from ethyl acetate/petroleum ether. The title compound is obtained in the form of white crystals with a melting point of 183°-184° C. and with Rf=0.37 on thin-layer silica gel plates in the system methylene chloride/methanol (10:1).
Workup
- customExcess sodium hydride is destroyed with methanol
- customThe residue is partitioned repeatedly between ethyl acetate
- dry with materialThe organic phases are dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customthe residue is crystallised from ethyl acetate/petroleum ether
Sources & evidence
- ORD record
- ord-270eb2b77fe046e2beac6154de4a193f
- Source dataset
- uspto-grants-1989_06
- Patent number
- US04839379
Reaction notes
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