Dimethylformamide → 3-Isoxazolecarboxylic acid, 4-(4-hydroxyphenyl)-5-methyl-, ethyl ester

HRID 922210Notes

Reaction equation

HRID 922210 reaction equation
CN(C=O)C.[OH:6][C:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1.I[C:17]1[C:18]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:19][O:20][C:21]=1[CH3:22].C(=O)(O)[O-].[Na+]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[OH:6][C:7]1[CH:12]=[CH:11][C:10]([C:17]2[C:18]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:19][O:20][C:21]=2[CH3:22])=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 666859623-Isoxazolecarboxylic acid, 4-iodo-5-methyl-, ethyl ester

Product 1

HCID 666855843-Isoxazolecarboxylic acid, 4-(4-hydroxyphenyl)-5-methyl-, ethyl esterYield 57.8%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 25 mL RB flask fitted with a magnetic stirrer was charged with DMF (2.5 mL). To the stirred solvent were added 4-hydroxyphenylboronic acid (0.2 g, 0.7 mmol), ethyl 4-iodo-5-methyl-1,2-oxazole-3-carboxylate (0.116 g, 0.8 mmol), sodium bicarbonate (0.18 g, 2.1 mmol) and water (0.08 mL) under argon atmosphere. After addition, the reaction mixture was purged with argon for 15 minutes. To this bis(triphenylphosphine)palladium (II) chloride (0.05 g, 0.07 mmol) was added and purged with argon for 10 minutes. After addition, the reaction mixture was heated at 95° C. for 5 h under argon atmosphere. After completion of the reaction, the reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (10 mL). The organic layer was washed with water (5 mL) and brine solution (5 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude was purified through silica gel column chromatography using ethyl acetate and petroleum ether as elutants. The product was obtained as an off white solid (0.1 g, yield: 57%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.13 (d, 2H), 6.80-6.82 (d, 2H), 5.14 (s, 1H), 4.25-4.32 (q, 2H), 2.36 (s, 3H), 1.23-1.28 (t, 3H).

Workup

  1. customTo a 25 mL RB flask fitted with a magnetic stirrer
  2. additionAfter addition
  3. customthe reaction mixture was purged with argon for 15 minutes
  4. custompurged with argon for 10 minutes
  5. additionAfter addition
  6. customAfter completion of the reaction
  7. customthe reaction mixture was quenched with water (10 mL)
  8. extractionextracted with ethyl acetate (10 mL)
  9. washThe organic layer was washed with water (5 mL) and brine solution (5 mL)
  10. dry with materialThe organic layer was dried over anhydrous Na2SO4
  11. customthe solvent was removed under reduced pressure
  12. customThe crude was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-0b3ac48049a042969214a70c80350a11
Source dataset
uspto-grants-2016_03
Patent number
US09278915B2

Reaction notes

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