Acetic Acid → HCID 68956458, compound

HRID 2378071Notes

Reaction equation

HRID 2378071 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[N:17][OH:18])[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.C([Li])CCC.[CH3:24][O:25][C:26]([C:28]1([C:31](OC)=[O:32])[CH2:30][CH2:29]1)=[O:27].C(O)(=O)C>O1CCCC1.O>[CH3:24][O:25][C:26]([C:28]1([C:31]2([OH:32])[O:18][N:17]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[CH:10]2[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:30][CH2:29]1)=[O:27]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 27695391,1-Cyclopropanedicarboxylic acid, 1,1-dimethyl esterHCID 76529953HCID 76529953, compoundHCID 178418339Butyllithium

Product 1

HCID 68956458HCID 68956458, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(4-Methoxy-phenyl)-2-phenyl-ethanone oxime, which may be produced as in Example 137 (110 g, 456 mmol, 1 equiv) is dissolved in tetrahydrofuran (825 mL), and the solution is cooled to about 0 □C in an ice/isopropyl alcohol bath. Butyllithium (2.5 M in hexane, 383 mL, 957 mmol, 2.1 equiv) is added at a rate to keep the temperature below 10 □C (about 1 hour addition time). The solution is allowed to stir for about 15 minutes. Cyclopropane-1,1-dicarboxylic acid dimethyl ester (86.5 g, 547 mmol, 1.2 equiv.) is added rapidly, and the reaction is allowed to stir for about 15 minutes. The reaction is quenched by the addition of acetic acid (65.3 mL, 1140 mmol, 2.5 equiv), and water (200 mL) is added. The mixture is allowed to sit overnight. The water layer is removed, and the organic layer is washed with water (300 mL). Toluene (100 mL) is added, and the organic layer is concentrated to give crude title compound, 1-[5-hydroxy-3-(4-methoxy-phenyl)-4-phenyl-4,5-dihydro-isoxazol-5-yl]-cyclopropanecarboxylic acid methyl ester, which may be used without purification.

Workup

  1. temperaturethe solution is cooled to about 0 □C in an ice/isopropyl alcohol bath
  2. additionbelow 10 □C (about 1 hour addition time)
  3. stirringto stir for about 15 minutes
  4. additionis added
  5. waitto sit overnight
  6. customThe water layer is removed
  7. washthe organic layer is washed with water (300 mL)
  8. additionToluene (100 mL) is added
  9. concentrationthe organic layer is concentrated

Sources & evidence

ORD record
ord-e179e68999414aa1aea4d88fb6cae8c0
Source dataset
uspto-grants-2008_12
Patent number
US07470715B2

Reaction notes

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