Potassium Carbonate → Ethyl 2-[4-(hydroxymethyl)phenyl]-1,3-oxazole-4-carboxylate

HRID 1716824Notes

Reaction equation

HRID 1716824 reaction equation
F[B-](F)(F)F.C([PH+]([C:15]([CH3:18])(C)C)C(C)(C)C)(C)(C)C.Cl[C:20]1[N:21]=[C:22]([C:25]([O-])=O)[O:23][CH:24]=1.[OH:28][CH2:29][C:30]1[CH:35]=[CH:34]C(B(O)O)=[CH:32][CH:31]=1.[C:39](=O)([O-:41])[O-:40].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:28][CH2:29][C:30]1[CH:31]=[CH:32][C:25]([C:22]2[O:23][CH:24]=[C:20]([C:39]([O:41][CH2:15][CH3:18])=[O:40])[N:21]=2)=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 11430Potassium Carbonate2×HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 131728347Chlorooxazole carboxylate

Product 1

HCID 46834789Ethyl 2-[4-(hydroxymethyl)phenyl]-1,3-oxazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
86 °C

Procedure

To a suspension of tris(dibenzylideneacetone)dipalladium (0) (0.025 eq) and tri-tert-butylphosphonium tetrafluoroborate (0.05 eq) a mixture of dioxane and 1N aqueous potassium carbonate (3:1) degassed with nitrogen was added chlorooxazole carboxylate (1 eq) followed by a suspension of 4-hydroxymethylphenylboronic acid (1 eq) in a mixture of dioxane and 1N aqueous potassium carbonate (8:1) continuing to degas with nitrogen and the resulting reaction mixture was stirred at 86° C. (reflux) until determined complete by HPLC (about 2 h). The reaction mixture was allowed to cool to room temperature and filtered through celite, the organic layer separated, and the aqueous layer extracted with ethyl acetate. The dioxane layer was concentrated (avoiding total evaporation to dryness) and combined with the ethyl acetate extract and washed with aq. sodium bicarbonate, brine, dried over sodium sulphate, filtered, evaporated, and triturated with MTBE. The isolated yield of the target compound was 68%. m.p. 99-101° C.; 1H NMR (300 MHz, CDCl3, δ): 8.27 (s, 1H), 8.10 (d, 2H, J=8.2 Hz), 7.47 (d, 2H, J=8.2 Hz), 4.77 (s, 2H), 4.43 (m, 2H, J=7.4 Hz), 1.41 (t, 3H, J=7.4 Hz).

Workup

  1. customdegassed with nitrogen
  2. customto degas with nitrogen
  3. customthe resulting reaction mixture
  4. temperature(reflux)
  5. customuntil determined complete by HPLC (about 2 h)
  6. temperatureto cool to room temperature
  7. filtrationfiltered through celite
  8. customthe organic layer separated
  9. extractionthe aqueous layer extracted with ethyl acetate
  10. concentrationThe dioxane layer was concentrated
  11. custom(avoiding total evaporation to dryness)
  12. extractionextract
  13. washwashed with aq. sodium bicarbonate, brine
  14. dry with materialdried over sodium sulphate
  15. filtrationfiltered
  16. customevaporated
  17. customtriturated with MTBE

Sources & evidence

ORD record
ord-55cd84f06af74cb7b11c9ded2db8225c
Source dataset
uspto-grants-2010_09
Patent number
US07803825B2

Reaction notes

Loading…