4-(2,2-Dimethoxyethylcarbamoyl)phenyl acetate → 4-(Oxazol-2-yl)phenyl methanesulfonate

HRID 630332Notes

Reaction equation

HRID 630332 reaction equation
C([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:19])[NH:12][CH2:13][CH:14](OC)OC)=[CH:7][CH:6]=1)(=O)C.[CH3:20][S:21](O)(=[O:23])=[O:22].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>CCOC(C)=O>[CH3:20][S:21]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[O:19][CH:14]=[CH:13][N:12]=2)=[CH:9][CH:10]=1)(=[O:23])=[O:22]

Participants

4

Reactant 2

HCID 117475554-(2,2-Dimethoxyethylcarbamoyl)phenyl acetateHCID 86584057Phosphorus Pentoxide-Methanesulfonic Acid

Product 1

HCID 109226274-(Oxazol-2-yl)phenyl methanesulfonate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

In a similar manner as described in Pandit, C. R. et al., “Preparation of 2-Substituted Oxazoles”, Synth. Commun. 32, 2427-2432 (2002), 4-(2,2-dimethoxyethylcarbamoyl)phenyl acetate (43 g, 160.88 mmol) was stirred and treated with Eaton's reagent (380 ml; 7.7 wt. % phosphorus pentoxide in methanesulfonic acid, Aldrich #38,081-4). After 15 minutes, the internal temperature of the reaction was raised to about 130° C. and held for about 3 hours. The reaction was followed by TLC analysis (2:1 EtOAc:Hex) with only a single new UV active spot observed. The reaction mixture was allowed to cool to about 40° C. and was then cooled in an ice bath to about 3° C. The reaction was poured into 2 L of ice water and extracted with ethyl acetate (1.4 L). The organic layer was washed with water (1 L). The combined aqueous layers were extracted with ethyl acetate (2×1 L). The combined organic layers were washed with water (2×) and brine, dried, treated with silica gel and charcoal, and concentrated. The residue was dissolved in methylene chloride and treated with hexane until a precipitate was seen. The mixture was treated with charcoal, filtered, and concentrated to give 53.3 g of 4-(oxazol-2-yl)phenyl methanesulfonate (>100% th.; 90% pract.) which contained 1.2 equivalents of methyl methanesulfonic acid; 1H NMR (CDCl3) δ 8.07 (d, 2H), 7.71 (d, 1H), 7.36 (d, 2H), 7.22 (d, 1H), 3.16 (s, 3H) ppm.

Workup

  1. waitheld for about 3 hours
  2. temperatureto cool to about 40° C.
  3. temperaturewas then cooled in an ice bath to about 3° C
  4. extractionextracted with ethyl acetate (1.4 L)
  5. washThe organic layer was washed with water (1 L)
  6. extractionThe combined aqueous layers were extracted with ethyl acetate (2×1 L)
  7. washThe combined organic layers were washed with water (2×) and brine
  8. customdried
  9. additiontreated with silica gel and charcoal
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in methylene chloride
  12. additiontreated with hexane until a precipitate
  13. additionThe mixture was treated with charcoal
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-95657ac5edef45799a1bf4792d8aade5
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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