Dimethylformamide → Ethyl 3-(4-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylate

HRID 1625923Notes

Reaction equation

HRID 1625923 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([CH:6]=[N:7][OH:8])=[CH:4][CH:3]=1.ClN1[C:16](=[O:17])[CH2:15][CH2:14][C:13]1=O.ON=C(Cl)[C:22]1[CH:27]=CC(F)=CC=1.CN(C=[O:34])C>O>[CH2:27]([O:34][C:16]([C:15]1[C:6]([C:5]2[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)=[N:7][O:8][C:14]=1[CH3:13])=[O:17])[CH3:22]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 31398ChlorosuccinimideHCID 68017N-[(4-fluorophenyl)methylidene]hydroxylamineHCID 27563164-fluoro-N-hydroxybenzenecarboximidoyl chloride

Product 1

HCID 22309061Ethyl 3-(4-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of 4-fluoro-benzaldehyde oxime (1.39 g, 10.0 mmol) in DMF (10 mL) was added portionwise within 5 minutes at 15 to 20° C. N-chlorosuccinimide (1.36 g, 10.0 mmol) and the resulting mixture was stirred at room temperature for 90 minutes. The yellow solution (containing N-Hydroxy-4-fluoro-benzenecarboximidoyl chloride) was then treated within 2 minutes at room temperature with a solution of ethyl-3-(1-pyrrolidino)crotonate (1.89 g, 10.0 mmol) in 5 mL of DMF and the resulting solution was stirred at room temperature for 28 hours. The mixture was diluted with water (25 mL) and subsequently extracted with ethyl acetate (4×25 mL). The combined organic layers were washed with 1 M HCl (2×25 mL) and water (2×25 mL), dried over Na2SO4 and subsequently concentrated to dryness (45° C./25 mbar) to afford 2.37 g (95%) of the title ester as a brownish solid with a purity of 100% (by GC) and 97% (by HPLC).

Workup

  1. additionwas added portionwise within 5 minutes at 15 to 20° C
  2. extractionsubsequently extracted with ethyl acetate (4×25 mL)
  3. washThe combined organic layers were washed with 1 M HCl (2×25 mL) and water (2×25 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationsubsequently concentrated to dryness (45° C./25 mbar)

Sources & evidence

ORD record
ord-6725e7b30088453da7e6433f9f38bd73
Source dataset
uspto-grants-2014_07
Patent number
US08785435B2

Reaction notes

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