Toluene → [5-Cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol

HRID 2423409Notes

Reaction equation

HRID 2423409 reaction equation
[CH:1]1([C:6]2[O:10][N:9]=[C:8]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[C:7]=2[C:19](OCC)=[O:20])[CH2:5][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+]>O1CCCC1.C(OCC)(=O)C>[CH:1]1([C:6]2[O:10][N:9]=[C:8]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[C:7]=2[CH2:19][OH:20])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 9357Potassium Sodium TartrateHCID 21225700Diisobutylaluminumhydride2×HCID 59321583Ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate

Product 1

HCID 59709035[5-Cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanolYield 96.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (3.0 g, 8.6 mmol) in tetrahydrofuran (35 mL) at 0° C. was added a 1.5 M solution of diisobutylaluminum hydride in toluene (8.6 mL, 13 mmol) dropwise. The solution was allowed to stir while warming slowly for approximately 3.5 hours and was re-cooled to 0° C. An additional portion of diisobutylaluminum hydride (4.3 mL, 6.5 mmol) was added and the solution was allowed to stir for an additional 35 minutes. Then Rochelle's salt (40 mL) was added slowly at 0° C. followed by some ethyl acetate. The mixture was allowed to warm to ambient temperature and stirred overnight. The layers were separated and the ethyl acetate was washed with brine, dried over magnesium sulfate and concentrated to afford [5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol (2.59 g, 82%). 1H-NMR (400 MHz, DMSO-d6) δ 7.61-7.51 (m, 3H), 4.85 (t, J=5 Hz, 1H), 4.14 (d, J=5 Hz, 2H), 3.46-3.48 (m, 1H), 2.07-1.99 (m, 2H), 1.81-1.60 (m, 6H).

Workup

  1. temperaturewhile warming slowly for approximately 3.5 hours
  2. stirringto stir for an additional 35 minutes
  3. temperatureto warm to ambient temperature
  4. stirringstirred overnight
  5. customThe layers were separated
  6. washthe ethyl acetate was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0bd02ca00c9045e6835cac83358c76aa
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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