Triethylamine → Ammonium Hydroxide

Participants

Reaction Conditions

Reaction Steps

Add the product of step 2 (2.35 g) in methylene chloride (70 mL) dropwise to hexahydro-2H-1,4-diazepine (0.66 g, 6.6 mmol), triethylamine (1.38 mL, 9.9 mmol) in methylene chloride (35 mL) cooled to 0° C. over 10 minutes. Warm the reaction to room temperature for 30 minutes. Concentrate in vacuo to a yellow solid. Chromatograph the solid on a column of silica gel (500 g) eluting with 4:1:95 methanol:ammonium hydroxide:methylene chloride (2 L) to give the title compound, a free base (1.75 g) as a 6.5:1 mixture of isomers. Rf=0.52 5:95 methanol:methylene chloride containing 0.2% ammonium hydroxide). Dissolve the mixture of isomers in aqueous hydrochloric acid (5 mL, 1N) and concentrate to a white solid. Separate the isomers (100 mg) on a high pressure reversed-phase silica gel column (C18 Dynamax Semiprep 60A®, trademark of Rainin Instruments, Woburn, Mass. 01801) eluting with a 35:65 mixture of water:methanol buffered with 0.2% trifluoroacetic acid at a flow rate of 10 mL/minute to give 65 mg of the title compound.

Provenance & Evidence