Aluminium lithium hydride → 5-Cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-4-isoxazolemethanol

HRID 1748152Notes

Reaction equation

HRID 1748152 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH:7]1([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][C:22]([F:25])([F:24])[F:23])[C:11]=2[C:26](OC)=[O:27])[CH2:9][CH2:8]1>O1CCCC1>[CH:7]1([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][C:22]([F:25])([F:23])[F:24])[C:11]=2[CH2:26][OH:27])[CH2:8][CH2:9]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66906029Methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate

Product 1

HCID 669061975-Cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-4-isoxazolemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 250-mL round-bottom flask was purged with nitrogen and a suspension of LiAlH4 (2.5 g, 65.8 mmol, 2.87 equiv) in tetrahydrofuran (50 mL) was added. This was followed by the addition of a solution of methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate (7.5 g, 22.9 mmol, 1.00 equiv) in tetrahydrofuran (50 mL) dropwise at −10°C. The resulting reaction mixture was stirred fo(30 min at −10°C. When the reaction was complete, it was quenched by the addition of 3 mL of ethyl acetate, followed by 3 mL of water and O1 mL of 15% aqueous NaOH, all whilst maintaining a vigorous stirring. The resulting white precipitate was filtered through celite®, and the filter cake was washed with 200 mL of ethyl acetate. The filtrate was washed with brine (2×100 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 7 g of (5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanol as yellow oil. (1H-NM(300 MHz, CDCl3) δ 7.56 (m, 2H), 7.41 (m, 2H), 4.50 (s, 2H), 2.20 (m, 1H), 1.72 (s, 1H, —OH) 1.11-1.28 (m, 4H).

Workup

  1. customA 250-mL round-bottom flask was purged with nitrogen
  2. additionwas added
  3. customThe resulting reaction mixture
  4. custom30 min
  5. customat −10°C
  6. customit was quenched by the addition of 3 mL of ethyl acetate
  7. temperatureO1 mL of 15% aqueous NaOH, all whilst maintaining a vigorous stirring
  8. filtrationThe resulting white precipitate was filtered through celite®
  9. washthe filter cake was washed with 200 mL of ethyl acetate
  10. washThe filtrate was washed with brine (2×100 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated under vacuum
  13. customThis resulted in 7 g of (5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanol as yellow oil

Sources & evidence

ORD record
ord-f93dcd18f69e4466bbfca70343eb5261
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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