Drug info - Propylhexedrine synthesis

[Rita-Lynn]

PROPYLHEXEDRINE


Therapeutic Function: Nasal decongestant

Chemical Name: N,α-dimethylcyclohexaneethanamine

Common Name: Hexahydrodesoxyephedrine

Structural Formula:


Chemical Abstracts Registry No.: 101-40-6; 6192-98-9 (hydrochloride)

Trade Names:
Benzedrex (SKF, USA, 1949)
Oristan (Whitehall, USA)
Eggobesin (Fahlberg-List, E. Germany)
Eventin (Minden, W. Germany)

Raw Materials:

cyclohexylacetone
N-methylformamlde
sulfuric acid
sodium hydroxide

Manufacturing Process:

33.6 grams of cyclohexylacetone, a compound known to the art, dissolved in 13 grams of 85% formic acid is caused to interact with 72.0 grams of N-methylformamide at 160º-18OºC for 4 hours. This results in the formation of the formyl derivative of the amine, according to the following reaction:

 
C6H11-CH2-C-CH3 + 2 HCONHCH3 -> C6H11-CH2-CH-CH3 + CH3NH2 + CO2
          ||                              |
          O                               NCH3
                                          |
                                          CHO

The formyl derivative is then hydrolyzed by refluxing with 50% sulfuric acid for about 4 hours, after which the hydrolysate is extracted with ether to remove the acid-insoluble material and the aqueous solution made strongly alkaline with any suitable alkalizing agent, for example, sodium hydroxide, to liberate the amine.

The amine is then taken up in ether, dried over potassium hydroxide and purified by distillation, preferably under reduced pressure. β-cycohexylisopropylmethylamine thus obtained boils at 90º-92ºC at 22mmHg.

References:
Merck Index 7761
Kleeman & Engel p.774
OCDS Vol.1 p.37 (1977)
I.N. p.817

Reputation Comments on this post:

	Thank you for posting synths on DF! We need more info of this nature.
	Thanks !