Toluene → (3,5-Dicyclopentyl-4-isoxazolyl)methanol

HRID 2423479Notes

Reaction equation

HRID 2423479 reaction equation
[CH:1]1([C:6]2[C:10]([C:11](OCC)=[O:12])=[C:9]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[O:8][N:7]=2)[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+]>C1COCC1>[CH:1]1([C:6]2[C:10]([CH2:11][OH:12])=[C:9]([CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[O:8][N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 9357Potassium Sodium TartrateHCID 21225700Diisobutylaluminumhydride2×HCID 59321558Ethyl 3,5-dicyclopentyl-4-isoxazolecarboxylate

Product 1

HCID 59321586(3,5-Dicyclopentyl-4-isoxazolyl)methanolYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 3,5-dicyclopentyl-4-isoxazolecarboxylate (1.57 g, 5.67 mmol) in THF (15.7 mL) was stirred in an ice bath as a 1.5 M solution of diisobutylaluminum hydride in toluene (8.1 mL, 12.1 mmol) was added dropwise. The solution was allowed to stir at 0° C. for 30 minutes then at room temperature for 5.5 hours. An additional portion of diisobutylaluminum hydride (1.6 mL, 2.4 mmol) was added and the solution was allowed to stir for 45 minutes. The solution was cooled in ice bath before the addition of a 10% aqueous solution of Rochelle's salt. The resulting solution was allowed to stir overnight. The solution was extracted with ethyl acetate and the organic layer was dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (silica gel, 3:7 ethyl acetate:hexanes) to provide (3,5-dicyclopentyl-4-isoxazolyl)methanol (0.80 g, 57% as 0.15 ethyl acetate). 1H NMR (400 MHz, DMSO-d6): δ 4.84 (s, 1H), 4.26 (d, J=4 Hz, 2H), 3.30-3.22 (m, overlapping H2O), 3.13-3.06 (m, 1H), 1.98-1.87 (m, 4H), 1.74-1.56 (m, 12H).

Workup

  1. additionwas added dropwise
  2. waitat room temperature for 5.5 hours
  3. stirringto stir for 45 minutes
  4. temperatureThe solution was cooled in ice bath
  5. stirringto stir overnight
  6. extractionThe solution was extracted with ethyl acetate
  7. dry with materialthe organic layer was dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography (silica gel, 3:7 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-74bb9ed4839847d7912497976b7926d1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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