Chloroform → Romazarit

HRID 623209Notes

Reaction equation

HRID 623209 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH2:14][OH:15])=[C:11]([CH3:13])[N:12]=2)=[CH:4][CH:3]=1.[OH-:16].[Na+].C(Cl)(Cl)Cl>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]([CH2:14][O:15][C:5]([CH3:6])([CH3:4])[C:8]([OH:9])=[O:16])=[C:11]([CH3:13])[N:12]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6212ChloroformHCID 14798Sodium HydroxideHCID 5064160HCID 5064160, compound

Product 1

HCID 71321RomazaritYield 65%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

6.9 g (30.8 mmol) of 2-(4-chlorophenyl)-4-methyl-5-oxazolemethanol were combined with 6.2 g (155 mmol) of powdered sodium hydroxide in 45 ml of acetone and the suspension was heated to reflux. 4.9 g (41.1 mmol) of chloroform in 10 ml of acetone were added dropwise during 30 minutes and the suspension was heated at reflux for 4 hours. The solvent was removed by evaporation under reduced pressure, and the residue was partitioned between 150 ml of diethyl ether and 400 ml of water. The organic phase was separated and the aqueous phase was extracted twice with diethyl ether. The aqueous phase was acidified to pH 2 with concentrated hydrochloric acid and extracted three times with 50 ml of dichloromethane each time. The combined dichloromethane extracts were dried over magnesium sulphate, filtered and evaporated to yield 3.7 g of crude product. Recrystallization from ethyl acetate yielded 3.1 g (32.5%) of 2-[[2-(4-chlorophenyl)-4 -methyl-5-oxazolyl]methoxy]-2-methylpropionic acid of melting point 166°-167° C.

Workup

  1. temperaturethe suspension was heated to reflux
  2. temperaturethe suspension was heated
  3. temperatureat reflux for 4 hours
  4. customThe solvent was removed by evaporation under reduced pressure
  5. customthe residue was partitioned between 150 ml of diethyl ether and 400 ml of water
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted twice with diethyl ether
  8. extractionextracted three times with 50 ml of dichloromethane each time
  9. dry with materialThe combined dichloromethane extracts were dried over magnesium sulphate
  10. filtrationfiltered
  11. customevaporated
  12. customto yield 3.7 g of crude product
  13. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-2db90f701e0544dba49af50befef5da4
Source dataset
uspto-grants-1988_09
Patent number
US04774253

Reaction notes

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