Hydrochloric Acid → 2-(4-Iodophenyl)oxazole

HRID 428572Notes

Reaction equation

HRID 428572 reaction equation
CS(O)(=O)=O.CO[CH:8]([O:20]C)[CH2:9][NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][CH:13]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].[Na+].CS(OC)(=O)=O.Cl>O1CCCC1.O>[I:18][C:15]1[CH:14]=[CH:13][C:12]([C:11]2[O:20][CH:8]=[CH:9][N:10]=2)=[CH:17][CH:16]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 4156Methyl MethanesulfonateHCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 10903782N-(2,2-dimethoxyethyl)-4-iodobenzamide

Product 1

HCID 98602582-(4-Iodophenyl)oxazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

Under an inert atmosphere, methanesulfonic acid (141 g, 1.46 mol) was added to a mixture of amide acetal (25 g, 74.6 mmol) and phosphorus pentoxide (25 g, 176 mmol). The reaction mixture was heated at 140° C. for about 12 hours. The reaction mixture was cooled to 0° C. and 150 mL of water was added while maintaining the reaction temperature below 40° C. The pH of the reaction mixture was adjusted to 12.5-13 with 50% sodium hydroxide and the reaction mixture was heated at ca. 45° C. to hydrolyze the carcinogenic byproduct methyl methanesulfonate. The reaction mixture was cooled to ambient temperature and 100 mL of tetrahydrofuran was added. The pH was adjusted to 5 with concentrated hydrochloric acid and the layers were separated. The spent aqueous phase was extracted twice with 100 mL of acetone. The rich organic extracts were combined and 200 mL of water was added to effect crystallization. The crystal slurry was filtered, washed and dried in vacuo at <50° C., to give 17 g (84 M %, HPLC area % >99) of the title compound.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. temperaturewhile maintaining the reaction temperature below 40° C
  3. temperaturethe reaction mixture was heated at ca. 45° C.
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. customthe layers were separated
  6. extractionThe spent aqueous phase was extracted twice with 100 mL of acetone
  7. addition200 mL of water was added to effect crystallization
  8. filtrationThe crystal slurry was filtered
  9. washwashed
  10. customdried in vacuo at <50° C.

Sources & evidence

ORD record
ord-09ef5616e89c404e839fb6d929e1f4bf
Source dataset
uspto-grants-2001_11
Patent number
US06313308B1

Reaction notes

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