Hydrochloric Acid → 2-Amino-4-methyl-5-(naphth-1-yl)oxazole

HRID 33559Notes

Reaction equation

HRID 33559 reaction equation
C(O[CH:5]([CH3:18])[C:6]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1)=[O:7])(=O)C.Cl.OC(C)C(C1C2C(=CC=CC=2)C=CC=1)=O.[N:35]#[C:36][NH2:37].[OH-].[Na+]>[Cl-].[Na+].O.O1CCCC1.O>[NH2:37][C:36]1[O:7][C:6]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)=[C:5]([CH3:18])[N:35]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 9864CyanamideHCID 14798Sodium HydroxideHCID 538227612-Hydroxy-1-naphthalen-1-yl-propan-1-oneHCID 597968292-Acetoxy-1-(naphth-1-yl)-1-propanone

Product 1

HCID 112761502-Amino-4-methyl-5-(naphth-1-yl)oxazoleYield 22.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of 2-acetoxy-1-(naphth-1-yl)-1-propanone (2.6 g), IMS (30 ml) and hydrochloric acid (1M; 22 ml) was boiled under reflux for 4 hours. The mixture was cooled, added to brine and extracted twice with dichloromethane. The combined organic extracts were dried with sodium sulphate, filtered and evaporated in vacuo to afford a mixture of crude 2-hydroxy-1-naphthalen-1-yl-propan-1-one and 1-hydroxy-1-naphthalen-1-yl-propan-1-one (B) as an oil (2.2 g). A portion of this material (0.5 g) was dissolved in tetrahydrofuran (2 ml) to which was added cyanamide (0.11 g), water (2 ml) and sodium hydroxide solution (2M; 0.25 ml). The mixture was stirred vigorously for 16 hours then tetrahydrofuran was added (10 ml). The mixture was heated to 40° C. for 30 minutes, cooled and left for a further 6 hours. Brine was added and the mixture was extracted twice with dichloromethane. The combined organic extracts were dried with sodium sulphate, filtered and evaporated in vacuo. The title compound (3) (0.13 g; m.p. 187-189° C.) was obtained following silica gel column chromatography of the residue in 50% ethyl acetate in petroleum ether.

Workup

  1. temperatureunder reflux for 4 hours
  2. temperatureThe mixture was cooled
  3. extractionextracted twice with dichloromethane
  4. dry with materialThe combined organic extracts were dried with sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford
  8. temperaturecooled
  9. waitleft for a further 6 hours
  10. extractionthe mixture was extracted twice with dichloromethane
  11. dry with materialThe combined organic extracts were dried with sodium sulphate
  12. filtrationfiltered
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-02256e10efc84aef96299bb2d3f2e60a
Source dataset
uspto-grants-2008_09
Patent number
US07429607B2

Reaction notes

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