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

HRID 1439516Notes

Reaction equation

HRID 1439516 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.[CH:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1>[C:1]1([C:7]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([CH2:16][CH:28]([OH:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 8058HexaneHCID 4104650N,5-Dimethyl-3-phenyl-4-isoxazolecarboxamideHCID 178418339Butyllithium

Product 1

HCID 203050053-phenyl-5-(beta-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

A suspension of 75 grams (0.348 mole) of 3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide in 1 liter of tetrahydrofuran is cooled to -65° C. and 478 milliliters of 1.6M n-butyllithium in hexane (0.765 mole) is added dropwise maintaining the temperature between -60° C. and -70° C. After the addition is complete, the orange suspension is stirred for 11/2 hours at -60° C. to -70° C., and then 37.2 grams (0.350 mole) of benzaldehyde in 375 milliliters tetrahydrofuran is added dropwise maintaining the temperature between -60° C. and -70° C. After addition is complete, the mixture is stirred 11/2 hours at -60° C. 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 percent 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-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide, m.p. 183° - 184° C.

Workup

  1. temperaturemaintaining the temperature between -60° C. and -70° C
  2. additionAfter the addition
  3. temperaturemaintaining the temperature between -60° C. and -70° C
  4. additionAfter addition
  5. stirringthe mixture is stirred 11/2 hours at -60° C. to -70° C.
  6. temperaturewarmed to -30° C.
  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 percent 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-90720d4d144c48d883dc6d685275a0ef
Source dataset
uspto-grants-1977_11
Patent number
US04060533

Reaction notes

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