Ethyl Acetate → [5-Cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol

HRID 646007Notes

Reaction equation

HRID 646007 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[C:18](OCC)=[O:19])[CH2:4][CH2:3][CH2:2]1.[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].C(OCC)(=O)C>O1CCCC1.C1(C)C=CC=CC=1>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=3[Cl:16])[C:6]=2[CH2:18][OH:19])[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 9357Potassium Sodium TartrateHCID 21225700Diisobutylaluminumhydride2×HCID 59264874Ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate

Product 1

HCID 59264868[5-Cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (1.5 g, 4.47 mmol) in tetrahydrofuran (20 mL) at 0° C. was added a 1.5 M solution of diisobutylaluminum hydride in toluene (6.3 mL, 9.39 mmol) slowly. The solution was allowed to warm slowly to ambient temperature and after 4 hours the solution was re-cooled to 0° C. and additional 1.5 M diisobutylaluminum hydride in toluene was added (6 mL, 9 mmol). The solution was allowed to stir with the flask in the ice bath for 1.5 h. Some aqueous Rochelle's salt was added dropwise followed by ethyl acetate. The mixture was stirred overnight and the phases were separated. The aqueous phase was extracted one more time with ethyl acetate. The combined organic phases were washed with Rochelle's salt, then brine, dried over MgSO4 and concentrated in vacuo to yield a white solid. (1.3 g, 98%). 1H-NMR (DMSO-d6,) δ 7.61-7.51 (m, 3H), 4.87 (t, J=5 Hz, 1H), 4.10 (d, J=5 Hz, 2H), 3.87 (quintet, J=9 Hz, 1H), 2.37-2.30 (m, 4H), 2.29-1.87 (m, 2H).

Workup

  1. temperaturewas re-cooled to 0° C.
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted one more time with ethyl acetate
  4. washThe combined organic phases were washed with Rochelle's salt
  5. dry with materialbrine, dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto yield a white solid

Sources & evidence

ORD record
ord-7dd5cd6661cb4c37964d7e3682cc3b4c
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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