Toluene → (5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methanol

HRID 2423455Notes

Reaction equation

HRID 2423455 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:19])[C:6]=2[C:20](OCC)=[O:21])[CH2:4][CH2:3][CH2:2]1.[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(OCC)(=O)C>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:13]([CH3:19])=[CH:14][CH:15]=[CH:16][C:17]=3[CH3:18])[C:6]=2[CH2:20][OH:21])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 9357Potassium Sodium TartrateHCID 21225700DiisobutylaluminumhydrideHCID 59321517Ethyl 5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolecarboxylate

Product 1

HCID 59321504(5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methanolYield 100%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolecarboxylate (1.08 g, 3.26 mmol) at 0° C. was added a 1.5 M solution of diisobutylaluminum hydride in toluene (7.18 mL, 10.8 mmol) at a slow pace. The solution was allowed to stir while warming slightly for approximately 1.5 hours and then was re-cooled to 0° C. Then approximately 40 mL of Rochelle's salt was slowly added followed by ethyl acetate. The mixture was allowed to warm to ambient temperature and stirred overnight. Then the layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated to afford (5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methanol (937 mg, 100%). 1H-NMR (400 MHz, DMSO-d6) δ 7.03-6.91 (m, 3H), 4.97 (t, J=5 Hz, 1H), 4.83 (s, 2H), 4.35 (d, J=5 Hz, 2H), 3.85-3.77 (m, 1H), 2.36-2.26 (m, 4H), 2.14 (s, 6H), 2.10-1.98 (m, 1H), 1.94-1.84 (m, 1H).

Workup

  1. temperaturewhile warming slightly for approximately 1.5 hours
  2. temperatureto warm to ambient temperature
  3. stirringstirred overnight
  4. customThen the layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d82b3d1b739a485ab9582d29184e5119
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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