Benzaldehyde → 3-Ethyl-5-(2-hydroxy-2-phenylethyl)-N-methyl-1,2-oxazole-4-carboxamide

HRID 1112207Notes

Reaction equation

HRID 1112207 reaction equation
[CH2:1]([C:3]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[C:6]([CH3:12])[O:5][N:4]=1)[CH3:2].C([Li])CCC.CCCCCC.[CH:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCCC1>[CH2:1]([C:3]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[C:6]([CH2:12][CH:24]([OH:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:5][N:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 8058HexaneHCID 203488493-Ethyl-N,5-dimethyl-1,2-oxazole-4-carboxamideHCID 178418339Butyllithium

Product 1

HCID 203488383-Ethyl-5-(2-hydroxy-2-phenylethyl)-N-methyl-1,2-oxazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A suspension of 58.5 g. (0.348 mole) of 3-ethyl-N,5-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 suspension is stirred for 1 1/2 hours at -60° to -70° C., and then 37.2 g. (0.350 mole) of benzaldehyde in 375 ml. tetrahydrofuran is added dropwise maintaining the temperature between -60° and -70° C. After addition is complete, the mixture is stirred for 1 1/2 hours 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 mangesium sulfate, filtered and evaporated in vacuo. The solid residue is triturated with ether and filtered to give 3-ethyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide, m.p. 135° to 137° C.

Workup

  1. additionA suspension of 58.5 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. stirringthe mixture is stirred for 1 1/2 hours at -60° to -70° 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% brine
  11. dry with materialonce with brine, dried over anhydrous mangesium sulfate
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customThe solid residue is triturated with ether
  15. filtrationfiltered

Sources & evidence

ORD record
ord-bb76e891d29e43d3a5d4e5d6db8c7752
Source dataset
uspto-grants-1978_10
Patent number
US04120967

Reaction notes

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