Triethylamine → 4-Oxazolecarboxylic acid, 5-[4-(trifluoromethyl)phenyl]-, ethyl ester

HRID 1672583Notes

Reaction equation

HRID 1672583 reaction equation
C(N(CC)CC)C.[F:8][C:9]([F:20])([F:19])[C:10]1[CH:18]=[CH:17][C:13]([C:14](Cl)=[O:15])=[CH:12][CH:11]=1.[N+:21]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])#[C-:22]>C1COCC1>[F:8][C:9]([F:20])([F:19])[C:10]1[CH:18]=[CH:17][C:13]([C:14]2[O:15][CH:22]=[N:21][C:23]=2[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 533707Ethyl isocyanoacetate

Product 1

HCID 27394814-Oxazolecarboxylic acid, 5-[4-(trifluoromethyl)phenyl]-, ethyl esterYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (10.0 mL, 71.9 mmol) was added to a solution of 4-(trifluoromethyl)benzoyl chloride (5.0 g, 24.0 mmol) in THF (50 mL) at 0° C. Ethyl 2-isocyanoacetate (2.9 mL, 26.4 mmol) was added dropwise and the mixture was warmed to ambient temperature. After 3.5 days the reaction mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The separated aqueous phase was extracted with EtOAc, and the combined organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Chromatography on silica gel (Analogix® Intelliflash 280™; SF40-150 g column; 20% to 50% EtOAc/hexanes eluant, 30 min) yielded 4.30 g (63%) of the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.18 (d, J=8.2, 2H), 7.92 (d, J=8.3, 2H), 4.31 (q, J=7.1, 2H), 1.28 (t, J=7.0, 3H). MS (DCI+) m/z 286 (M+H).

Workup

  1. customAfter 3.5 days the reaction mixture was partitioned between EtOAc (100 mL) and H2O (100 mL)
  2. extractionThe separated aqueous phase was extracted with EtOAc
  3. washthe combined organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2582535e40dd4b729a955172cee88445
Source dataset
uspto-grants-2011_08
Patent number
US07998993B2

Reaction notes

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