Phosphorus oxychloride → Ethyl 5-methyl-1,3-oxazole-2-carboxylate

HRID 2200584Notes

Reaction equation

HRID 2200584 reaction equation
O=[C:2]([NH:8][CH2:9][C:10](=[O:12])[CH3:11])[C:3]([O:5][CH2:6][CH3:7])=[O:4].P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:11][C:10]1[O:12][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[N:8][CH:9]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 57348900Ethyl oxo[(2-oxopropyl)amino]acetate

Product 1

HCID 22099282Ethyl 5-methyl-1,3-oxazole-2-carboxylateYield 44.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of ethyl 2-oxo-2-(2-oxopropylamino)acetate (1.7 g, 9.8 mmol) in toluene (10 mL) was added phosphorus oxychloride (2 mL). The mixture was heated to reflux for 3 h. The reaction was concentrated to dryness and the residue was taken up in ethyl acetate (20 mL). This organic phase was washed with saturated aqueous sodium bicarbonate solution and brine, dried and concentrated to give a crude product which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (4:1) to give ethyl 5-methyloxazole-2-carboxylate (0.68 g, 44.1% yield) as yellow syrup. 1H-NMR (CDCl3) δ 6.97 (s, 1H), 4.44-4.49 (q, 2H), 2.43 (s, 3H), 1.42-1.46 (t, 2H). LCMS retention time 0.643 min; LCMS MH+ 156.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 3 h
  3. concentrationThe reaction was concentrated to dryness
  4. washThis organic phase was washed with saturated aqueous sodium bicarbonate solution and brine
  5. customdried
  6. concentrationconcentrated
  7. customto give a crude product which
  8. customwas purified via silica gel chromatography
  9. washeluting with petroleum ether/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-de54447bfc9843e7848a731c4976aebc
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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