HCl and other salts
HCl salt to free base:
To a stirred suspension of the amine HCl salt (0.2 mol) in dichloromethane was added aqueous solution of NaHCO3 (0.4 mol) in 300 mL water. The mixture was stirred for 30 minutes at room temperature until it became a clear solution. The organic layer was separated, dried (Na2SO4) and evaporated. To recover more product from the aqueous layer it was saturated with sodium chloride, 500 mL dichloromethane was added and stirred at room temperature for overnight (12 h) to give the corresponding amine in a total of 92% yield.
Free base to HCl salt:
To a solution of the amine (0.001 mol) in 2 mL dichloromethane was added 4 mL 2M HCl solution in diethyl ether. The mixture was stirred at room temperature for 10 minutes. The solvent was evaporated, residue was triturated with ether, and solid precipitated was filtered, washed with ether and dried to give the corresponding HCl salt in 70% yield.
Another example:
Reference: US Patent 5,324,732 (a great ref. for many kind of salt preparation)
Can you determine whether the HCl salt is formed through nmr methods?
sks
April 25, 2008 at 6:45 pm
I have never taken NMR of the HCl salts. We took the NMR of the pure free bases and then LC-MS of the salts (of course Mass only shows the peaks for free bases). In most cases free bases were oils whereas the salts were solids. But I believe the fumarate salt can be characterized by NMR.
pmgb
April 25, 2008 at 7:11 pm
I’m working on boc deprotection and I’m trying to avoid the traditional DCM/TFA treatment. What is the best way for preparing HCl in ether. I heard of boiling hydrochloric acid through CaCl2 and then bubbling the HCl gas into ether. But that will take glasswear and a set-up that I don’t have. Also, how long is the HCl-ether good for after its made?
Patrick
July 2, 2008 at 4:06 pm
We use “Hydrogen chloride, 2.0 M solution in diethyl ether” available from Aldrich (Cat. No. 455180-800ML). You have to keep it in refrigerator immidiately after use (otherwise HCl gas leaks out to the atmosphere).
pmgb
July 2, 2008 at 5:54 pm
HCl in ether can be made by adding sulfuric acid to NaCl and bubbling the resulting HCl gas into the ether.
bw
October 9, 2008 at 6:58 pm
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January 18, 2009 at 6:30 pm
Patrick,
Another option is ethanolic HCl, easily prepared by the (slow) addition of acetyl chloride to ethanol. To the protected amine in a minimal amount of ethanol add slight excess of the HCl solution (I prepare a 2N solution, keeps well on the shelf) and reflux ~20 min. Often nice crystals can be precipitated (after filtration!) with the addition of ether and cooling, or in the fridge overnight.
Steve
February 5, 2009 at 5:47 am
Thank you. How much acetyl chloride you add to how much ethanol to make 2N ethanolic HCl?
pmgb
February 5, 2009 at 6:16 pm