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	Notes on the synthesis of Chloroephedrine and the reduction thereof
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From Noggle, et al. (NARCOSWINE ALERT!) Anal-Chem, 58(8):1643, 1986:

General Method for the Preparation of the 1-Phenyl-1-chloro-2-(methylamino)
propanes (I).  A solution of the ephedrine hydrochloride or pseudoephedrine
hydrochloride (1.65 g, 10 mol) and thinyl chloride (10 mL) in chloroform
(200 mL) was stirred at reflux for 3 h.  The reaction solution was then
cooled to room temperature and the solvent vlume reduced to approximately
50 mL.  Adition of anhydrous ether (200 mL) followed by cooling (freezer)
resulted in crystallization of (I) HCl.

General Method for Perparation of the Methamphetamines.  A mixture of the
(I) HCl (500 mg, 2.3 mmol), sodium acetate trihydrate (1.22 g, 8.9 mmol),
and 5% Pd-BaSO4 (250mg) in glacial acetic acid (95 mL) and water (5 mL) was
shaken under a hydrogen atmosphere (intiial psi of 40-45) on a Parr
apparatus for 30-60 min.  After the uptake of hydrogen ceased, the catalyst
was removed by filtration and washed with water (50 mL).  The combined
filtrate and water washings were evaportaed to dryness under reduced pressure
and the remaining oil dissolved in water (50 mL), and acidified with
concentrated HCl (pH 1).  The acidic aqueous solution was washed with
chloroform (2 x 50 mL), then made basic (pH 12) with 10% NaOH.  The basic
aq solution was extracted with chloroform (3 x 75 mL), and the combined
extracts were washed with water (100 mL) and dried over MgSO4.  Evaporation
of the CHCl3 under reduced pressure yielded the product as the free base.
The base was coverted to the HCl salt in ethereal HCl, and the salt
was recrystallized from ethanol-ether to give a granular white solid.

And not only is there a narcoswine alert, but you get to play "find the
typos!"  I deliberately left some easy ones in there, to make you think 
about if that "5 mL" should really read "50 mL", or whatever. 

-- 
Lamont Granquist (lamontg at u dot washington dot edu)
ICBM: 47 39'23"N 122 18'19"W
"It all comes from here, the stench and the peril."--Frodo (from Perl5/toke.c)


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Tetrahedron: Assymmetry 9 1661-1671 (1998)
Chlorination of Ephedrine and Phenylpropanolamine

1-Chloro-1-phenyl-2-aminopropane hydrochloride 

To 1 gram (6.61 mmol) of norephedrine, 1.43 ml (19.8 mmol) of thionyl chloride 
was added. After stirring for 5 hours at room temp the excess thionyl chloride 
was removed under vacuum. The white solid obtained was washed with acetone, 
filtered and recrystallized from MeOH to yield 0.76 g (74%) of 
1-chloro-1-phenyl-2-aminopropane hydrochloride, mp 205-207°C. 

1-Chloro-1-phenyl-2-(N-methyl)aminopropane hydrochloride (Chloroephedrine)

The same general procedure as above was employed, using 3.0 g (18.1 mmol) of 
ephedrine and 3.9 ml (54.3 mmol) of thionyl chloride to give 3.7 g (94%) of 
chloroephedrine, mp 198-200°C. 

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