Trifluoroacetic acid → 3,9-Diazabicyclo[3.3.1]nonane-3-carboxylic acid, 9-methyl-7-oxo-, 1,1-dimethylethyl ester

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Reaction Steps

(4Benzyl-6-ethoxycarbonylmethyl-1-methylpiperazin-2-yl)acetic acid ethyl ester (Patent WO 92/05174) (71.0 g, 0.196 mol) was dissolved in MeOH (400 mL). TFA (77.8 mL, 1.02 mol) was added and the flask was purged with nitrogen. Pd/C (10%, 50% moisture, 3.6 g) was added. The flask was closed and purged with hydrogen (3×). After 1 day, the mixture was filtered through celite and washed with MeOH. The solvent was removed under reduced pressure and the foamy residue (92.7 g) was dried under high vacuum. A sol. of tBuOK (117.2 g, 1.04 mol) in toluene (3.07 L) was heated to reflux. A sol. of the crude piperazine formerly obtained, dissolved in THF (300 mL), was added dropwise over 50 min.

Provenance & Evidence