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

HRID 646013Notes

Reaction equation

HRID 646013 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]1[C:14]([C:15](OC)=[O:16])=[C:13]([CH:19]([CH3:21])[CH3:20])[O:12][N:11]=1.[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.[OH-].[Na+]>O1CCCC1.O.CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]1[C:14]([CH2:15][OH:16])=[C:13]([CH:19]([CH3:21])[CH3:20])[O:12][N:11]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 21225700DiisobutylaluminumhydrideHCID 59264879Methyl 3-[(2,6-dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolecarboxylate

Product 1

HCID 59264881[3-[(2,6-Dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolyl]methanolYield 99%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 3-[(2,6-dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolecarboxylate (1.18 g, 3.6 mmol) (from multiple batches) in tetrahydrofuran (10 mL) was stirred at 0° C. as a 1.5 M 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. Methanol (0.27 mL) was added followed by water (2.7 mL) then 2 N sodium hydroxide (4 mL). The solution was filtered through celite. The filtrate was partitioned between ethyl acetate and water. An aqueous solution of Rochelle's salt was added. The organic layer was separated, dried with magnesium sulfate, concentrated and purified by chromatography (silica gel, 30% ethyl acetate in hexane) to provide the title compound (1.07 g, 99%). 1H NMR (DMSO-d6): δ 7.46 (d, J=8 Hz, 2H), 7.32 (t, J=8 Hz, 1H), 5.01 (t, J=5 Hz, 1H), 4.36 (d, J=5 Hz, 2H), 4.22 (s, 2H), 3.21 (septet, J=7 Hz, 1H) 1.20 (d, J=7 Hz, 6H). ESI-LCMS m/z 300 (M+H)+.

Workup

  1. additionwas added
  2. filtrationThe solution was filtered through celite
  3. customThe filtrate was partitioned between ethyl acetate and water
  4. additionAn aqueous solution of Rochelle's salt was added
  5. customThe organic layer was separated
  6. dry with materialdried with magnesium sulfate
  7. concentrationconcentrated
  8. custompurified by chromatography (silica gel, 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1843581e57604247be646456a39b7b5d
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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