Trifluoroacetic acid → Ethyl 5-cyclobutyl-3-(hydroxymethyl)-4-isoxazolecarboxylate

HRID 2423453Notes

Reaction equation

HRID 2423453 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11]C(C)(C)C)[C:6]=2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][OH:11])[C:6]=2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59321584Ethyl 5-cyclobutyl-3-{[(1,1-dimethylethyl)oxy]methyl}-4-isoxazolecarboxylate

Product 1

HCID 59321537Ethyl 5-cyclobutyl-3-(hydroxymethyl)-4-isoxazolecarboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 5-cyclobutyl-3-{[(1,1-dimethylethyl)oxy]methyl}-4-isoxazole carboxylate (1.40 g, 5.48 mmol) in dichloromethane (250 mL) was added trifluoroacetic acid (250 mL, 3.25 mol). The solution was stirred for approximately 30 minutes and then concentrated. The residue was taken up with ethyl acetate and poured into water. The mixture was stirred as solid sodium carbonate was added until the pH was basic. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by chromatography (silica gel, 20% ethyl acetate in hexanes) to afford ethyl 5-cyclobutyl-3-(hydroxymethyl)-4-isoxazolecarboxylate (848 mg, 69%). 1H-NMR (400 MHz, DMSO-d6) δ 5.27 (t, J=6 Hz, 1H), 4.63 (d, J=6 Hz, 2H), 4.21 (q, J=7 Hz, 2H), 4.18-4.08 (m, 1H), 2.33-2.27 (m, 4H), 2.10-2.00 (m, 1H), 1.90-1.83 (m, 1H), 1.26 (t, J=7 Hz, 3H).

Workup

  1. concentrationconcentrated
  2. additionpoured into water
  3. stirringThe mixture was stirred as solid sodium carbonate
  4. additionwas added until the pH
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography (silica gel, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a8960113836641fa952a5fd80dd42d78
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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