Benzonitrile → 5-(2-amino-2-phenylethenyl)-N-methyl-3-phenyl-isoxazole-4-carboxamide

HRID 1763818Notes

Reaction equation

HRID 1763818 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:7][O:8][C:9]=1[CH3:10])=[O:4].C([Li])CCC.[C:22](#[N:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[NH2:29][C:22]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:10][C:9]1[O:8][N:7]=[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5]=1[C:3]([NH:2][CH3:1])=[O:4]

Participants

8

Reactant 4

HCID 7505BenzonitrileHCID 25517Ammonium ChlorideHCID 4104650N,5-Dimethyl-3-phenyl-4-isoxazolecarboxamideHCID 178418339Butyllithium

Product 1

HCID 46216675-(2-amino-2-phenylethenyl)-N-methyl-3-phenyl-isoxazole-4-carboxamideYield 63.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-5 °C

Procedure

A mixture of 100 grams (0.463 mole) of N,5-dimethyl-3-phenyl-isoxazole-4-carboxamide and 1000 milliliters of dry tetrahydrofuran is cooled to -5° C. While maintaining the temperature at -5° to 0° C., there is added over a period of 1 hour a solution of 435 grams (0.95 mole) of 15% n-butyllithium in hexane. The resulting mixture is stirred for 1 hour and while maintaining the temperature at -5° to 0° C. a solution of 50 grams (0.485 mole) of benzonitrile in 100 milliliters of dry tetrahydrofuran is added over a period of 1 hour. The resulting mixture is stirred for an additional hour at which time 100 milliliters of saturated ammonium chloride is added dropwise over a period of 15 to 20 minutes. The resulting solution is then mixed for 1 hour and 40 minutes and then diluted with 200 milliliters of water. The solids are then filtered off and washed three times with tetrahydrofuran/hexane. The solids are then dried under vacuum to give 94 grams of 5-(2-amino-2-phenylethenyl)-N-methyl-3-phenyl-isoxazole-4-carboxamide; m.p. 181° to 183° C. Further extraction from the mother liquors provide a total of 104 grams or 70.3% of the desired title compound. After further recrystallization from chloroform/methanol, the purified product has a melting point of 187° to 190° C.

Workup

  1. temperatureWhile maintaining the temperature at -5° to 0° C.
  2. additionis added over a period of 1 hour
  3. additionis added dropwise over a period of 15 to 20 minutes
  4. additionThe resulting solution is then mixed for 1 hour and 40 minutes
  5. filtrationThe solids are then filtered off
  6. washwashed three times with tetrahydrofuran/hexane
  7. customThe solids are then dried under vacuum

Sources & evidence

ORD record
ord-15228b6012ac4ca980a9b5fd9f63a85f
Source dataset
uspto-grants-1978_09
Patent number
US04113727

Reaction notes

Loading…