Toluene → [3-[2-(2,6-Dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methanol

HRID 1693665Notes

Reaction equation

HRID 1693665 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][CH2:10][C:11]1[C:15]([C:16](OC)=[O:17])=[C:14]([CH:20]([CH3:22])[CH3:21])[O:13][N:12]=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.CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][CH2:10][C:11]1[C:15]([CH2:16][OH:17])=[C:14]([CH:20]([CH3:22])[CH3:21])[O:13][N:12]=1

Participants

7

Reactant 4

HCID 1140Toluene2×HCID 9357Potassium Sodium TartrateHCID 21225700Diisobutylaluminumhydride2×HCID 59264851Methyl 3-[2-(2,6-dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolecarboxylate

Product 1

HCID 59264863[3-[2-(2,6-Dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methanolYield 96.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 3-[2-(2,6-dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolecarboxylate (0.900 g, 2.63 mmol) in THF (7.3 mL) was stirred at 0° C. as a 1.5M solution of diisobutylaluminum hydride in toluene (3.7 mL, 5.6 mmol) was added. The solution was allowed to warm to room temperature and stir overnight. Additional diisobutylaluminum hydride in toluene (1.8 mL, 2.7 mmol) was added and the solution was allowed to stir for another 3 hours. Methanol was added followed by a saturated aqueous solution of Rochelle's salt. The solution was stirred for two hours then was partitioned between ethyl acetate and brine. The organic layer was dried with magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-60% ethyl acetate in hexane) to provide the title compound (0.80 g, 51.6% as 0.25EtOAc). 1H NMR (DMSO-d6): 7.45 (d, J=8 Hz, 2H), 7.28 (t, J=8 Hz, 1H), 4.89 (t, J=5 Hz, 1H), 4.26 (d, J=5 Hz, 2H), 3.31-3.18 (m, 3H), 2.83-2.79 (m, 2H), 1.21 (d, J=7 Hz, 6H).

Workup

  1. additionwas added
  2. stirringto stir for another 3 hours
  3. stirringThe solution was stirred for two hours
  4. customthen was partitioned between ethyl acetate and brine
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. concentrationconcentrated
  7. custompurified by chromatography (silica gel, 0-60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d1bc44e91b57438daceb33d4c50d5c39
Source dataset
uspto-grants-2012_04
Patent number
US08158665B2

Reaction notes

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