4-Methylbenzaldehyde → 3-phenyl-5-(4-methyl-beta-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

HRID 2072197Notes

Reaction equation

HRID 2072197 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([CH3:16])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.CCCCCC.[C:28]1([CH3:36])[CH:33]=[CH:32][C:31]([CH:34]=[O:35])=[CH:30][CH:29]=1>O1CCCC1>[C:1]1([C:7]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([CH2:16][CH:34]([OH:35])[C:31]3[CH:32]=[CH:33][C:28]([CH3:36])=[CH:29][CH:30]=3)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 77254-MethylbenzaldehydeHCID 8058HexaneHCID 4104650N,5-Dimethyl-3-phenyl-4-isoxazolecarboxamideHCID 178418339Butyllithium

Product 1

HCID 203050573-phenyl-5-(4-methyl-beta-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A suspension of 75 g. (0.348 mole) of 3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide and 1 liter of tetrahydrofuran is cooled to -65° C. and 478 ml. of 1.6M n-butyllithium in hexane (0.765 mole) is added dropwise maintaining the temperature between -60° and -70° C. After the addition is complete, the orange suspension is stirred for 11/2 hours at -60° to -70° C., and then 37.2 g. (0.350 mole) of p-tolualdehyde in 375 ml. tetrahydrofuran is added dropwise maintaining the temperature between -60° and -70° C. After addition is complete the mixture is stirred for 11/2 hrs. at -60° to -70° C. and then warmed to -30° C. and quenched by the addition of saturated ammonium chloride solution. The mixture is further diluted with tetrahydrofuran and the layers are separated. The tetrahydrofuran layer is washed twice with 50% brine, and once with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The solid residue is triturated with a 50:50 mixture of ether:petroleum ether, filtered and washed with cold ether to give 3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide; m.p. 148° to 150° C.

Workup

  1. additionA suspension of 75 g
  2. temperaturemaintaining the temperature between -60° and -70° C
  3. additionAfter the addition
  4. temperaturemaintaining the temperature between -60° and -70° C
  5. additionAfter addition
  6. stirringis stirred for 11/2 hrs
  7. customquenched by the addition of saturated ammonium chloride solution
  8. additionThe mixture is further diluted with tetrahydrofuran
  9. customthe layers are separated
  10. washThe tetrahydrofuran layer is washed twice with 50% brine
  11. dry with materialonce with brine, dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customThe solid residue is triturated with a 50:50 mixture of ether
  15. filtrationpetroleum ether, filtered
  16. washwashed with cold ether

Sources & evidence

ORD record
ord-8c99e727fb11453698a5d5d3baf9fb7d
Source dataset
uspto-grants-1977_09
Patent number
US04049813

Reaction notes

Loading…