Methyl Acrylate → Methyl 3-[3-(trifluoromethyl)phenyl]4,5-dihydroisoxazole-5-carboxylate

HRID 1809923Notes

Reaction equation

HRID 1809923 reaction equation
[OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[CH:5]=1.[C:15]([O:19][CH3:20])(=[O:18])[CH:16]=[CH2:17]>C(Cl)Cl>[F:11][C:10]([F:13])([F:12])[C:6]1[CH:5]=[C:4]([C:3]2[CH2:17][CH:16]([C:15]([O:19][CH3:20])=[O:18])[O:1][N:2]=2)[CH:9]=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 7294Methyl AcrylateHCID 85444714HCID 85444714, compound

Product 1

HCID 57803314Methyl 3-[3-(trifluoromethyl)phenyl]4,5-dihydroisoxazole-5-carboxylateYield 105.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flask containing N-hydroxy-3-(trifluoromethyl)benzenecarboximidoyl chloride (2.0 g, 8.9 mmol) and methyl acrylate (0.7 g, 8 mmol) in methylene chloride (100 mL) at 0° C. under an inert atmosphere was added TEA (0.90 g, 8.8 mmol). The reaction mixture was slowly warmed to ambient temperature, stirred for 20 h, quenched with water (30 mL), and extracted with methylene chloride (2×50 mL). The organic extracts were combined, washed with saline solution (50 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel, eluting with methylene chloride/methanol (100/1 to 95/5). The appropriate fractions were combined and concentrated in vacuo to give methyl 3-[3-(trifluoromethyl)phenyl]-4,5-dihydroisoxazole-5-carboxylate (2.3 g, 100%): LCMS: 274.2 (M+H+, 100%); 1H NMR: (CDCl3) δ 8.03 (s, 1H), 7.92 (d, 1H), 7.71 (d, 1H), 7.59 (dd, 1H), 5.28 (dd, 1H), 3.86 (s, 3H), 3.71 (dd, 2H).

Workup

  1. customquenched with water (30 mL)
  2. extractionextracted with methylene chloride (2×50 mL)
  3. washwashed with saline solution (50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customchromatographed on silica gel
  7. washeluting with methylene chloride/methanol (100/1 to 95/5)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c04699c1dd3840b2afd6916e7b291520
Source dataset
uspto-grants-2013_01
Patent number
US08362003B2

Reaction notes

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