Diethyl nitromalonate → Methyl 5-phenyl-4-(3,3,3-trifluoropropyl)isoxazole-3-carboxylate

HRID 1804472Notes

Reaction equation

HRID 1804472 reaction equation
[F:1][C:2]([F:14])([F:13])[CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[N+:15]([CH:18](C(OCC)=O)[C:19]([O:21][CH2:22]C)=[O:20])([O-])=[O:16].F[P-](F)(F)(F)(F)F.C([N+]1C=CN(C)C=1)CCC>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:7]1([C:6]2[O:16][N:15]=[C:18]([C:19]([O:21][CH3:22])=[O:20])[C:5]=2[CH2:4][CH2:3][C:2]([F:13])([F:14])[F:1])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 97657Diethyl nitromalonateHCID 27341741-Butyl-3-methylimidazolium hexafluorophosphateHCID 58537198Benzene, (5,5,5-trifluoro-1-pentyn-1-yl)-

Product 1

HCID 67454167Methyl 5-phenyl-4-(3,3,3-trifluoropropyl)isoxazole-3-carboxylateYield 22.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (5,5,5-trifluoropent-1-ynyl)benzene (215 mg, 1.09 mmol), diethyl nitromalonate (0.758 mL, 4.34 mmol), and 1-butyl-3-methylimidazolium hexafluorophosphate (0.023 mL, 0.108 mmol) in toluene (3 mL) was heated to 170° C. for 150 minutes. The reaction mixture was diluted with ethyl acetate (50 mL), washed with water (10 mL), washed with brine (10 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by silica gel chromatography with hexanes/ethyl acetate (9/1) provided methyl 5-phenyl-4-(3,3,3-trifluoropropyl)isoxazole-3-carboxylate (72 mg). The compound had an HPLC ret. time=3.61 min.−Column. YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 ml/min; Solvent A=10% MeOH−90% Water−0.2% H3PO4; Solvent B=90% MeOH−10% water−0.2% H3PO4; Start % B=0; Final % B=100.

Workup

  1. washwashed with water (10 mL)
  2. washwashed with brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationConcentration
  5. customfollowed by purification by silica gel chromatography with hexanes/ethyl acetate (9/1)

Sources & evidence

ORD record
ord-7b6e50ec88564368b7715c8330c5648f
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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