Hydrochloric Acid → Pirbuterol hydrochloride

HRID 437394Notes

Reaction equation

HRID 437394 reaction equation
[OH:1][CH:2]([C:9]1[CH:10]=[CH:11][C:12]2[O:13]C(C3C=CC=CC=3)[O:15][CH2:16][C:17]=2[N:18]=1)[CH2:3][NH:4][C:5]([CH3:8])([CH3:7])[CH3:6].[ClH:25]>CC(C)=O.O>[ClH:25].[ClH:25].[OH:15][CH2:16][C:17]1[C:12]([OH:13])=[CH:11][CH:10]=[C:9]([CH:2]([OH:1])[CH2:3][NH:4][C:5]([CH3:7])([CH3:6])[CH3:8])[N:18]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 20223679HCID 20223679, compound

Product 1

HCID 68658Pirbuterol hydrochloride

Reagents, catalysts & solvents 1

HCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

One and five-tenths grams (4.8 m moles) of the above intermediate 6-(1-hydroxy-2-t-butylaminoethyl)-2-phenyl-4H-pyrido[3,2-d]-1,3-dioxin is dissolved in 20 ml. of acetone-water (1:1 v/v) and is treated with 1 ml. of 12N hydrochloric acid. After heating the solution to reflux for 5 hrs. the mixture is concentrated to an oil and dissolved in 100 ml. of ethanol. The water is azeotroped with 3 × 100 ml. portions of ethanol and the free base of the product generated by the addition of triethylamine. The solution is concentrated in vacuo to an oily slurry and the free base extracted from the triethylamine hydrochloride by extraction with acetone. The acetone extracts are combined, concentrated to an oil and the oil dissolved in 10 ml. of dry ethanol. Ethanol (.184 ml.) containing hydrogen chloride (188 gm. HCl/ml. ethanol) is added and the solution added dropwise to 2 l. of dry isopropyl ether. The product is filtered and dried, 1.05 g. Further purification by recrystallization from methanol-acetone provides 950 mg. of the product which by infrared and nuclear magnetic resonance spectroscopy and thin-layer chromatography are identical to that in U.S. Pat. No. 3,700,681.

Workup

  1. temperatureAfter heating the solution
  2. temperatureto reflux for 5 hrs
  3. concentrationthe mixture is concentrated to an oil
  4. dissolutiondissolved in 100 ml
  5. customThe water is azeotroped with 3 × 100 ml
  6. additionportions of ethanol and the free base of the product generated by the addition of triethylamine
  7. concentrationThe solution is concentrated in vacuo to an oily slurry
  8. extractionthe free base extracted from the triethylamine hydrochloride by extraction with acetone
  9. concentrationconcentrated to an oil
  10. dissolutionthe oil dissolved in 10 ml
  11. additionEthanol (.184 ml.) containing hydrogen chloride (188 gm
  12. additionethanol) is added
  13. additionthe solution added dropwise to 2 l
  14. filtrationThe product is filtered
  15. customdried
  16. customFurther purification
  17. customby recrystallization from methanol-acetone
  18. customprovides 950 mg

Sources & evidence

ORD record
ord-9ef7bc1665594cb681cc1be9ef17d858
Source dataset
uspto-grants-1977_06
Patent number
US04031108

Reaction notes

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