(R)-4-Boc-Piperazine-3-carboxylic acid

(2R)-l-(fc/^-Butoxycarbonyl)-4-isopropyIpiperazine-2-carboxylic acidTo (2i?)-l-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (4.5 g) and Na2CO3 (8.32 g) was added dry EtOH (135 ml) and isopropyl iodide (2.16 ml) and the mixture heated at reflux for 18 hours under argon. The solvent was then removed under reduced pressure, 5percentMeO?/DCM (50 ml) added, the mixture stirred for 1 hour in a stoppered flask, filtered and washed through with DCM (2 x 10ml). The filtrate was applied directly to a 12Og- silica Redisep cartridge and purified using 10-70percent MeOH/DCM. After evaporation, the product was isolated as a white foam (4.50 g), which was used without further purification. 1H NMR (400.132 MHz, DMSO) 0.95 (m, 6H), 1.40 (2x s, 9H), 2.30 (m, 2H), 2.75 (m, 2H), 2.95 (t, IH), 3.12 (t, IH, ), 3.70 (m, IH), 4.48 (d, IH), 12.60 (br. s, IH).te/t-Butyl (2R)-2-[(4-benzylpiperazin-l-yl)carbonyl]piperazine-l-carboxylate; 1-Benzylpiperazine (2.7ml) and (2R)-l-BOC-piperazine-2-carboxylic acid (3.57Ig) were suspended in DMF (150ml) and stirred at 00C. Triethylamine (4.33ml) was added followed by PyBOP reagent (8.08g). The mixture was allowed to warm to room temperature overnight, concentrated to approximately a third of the volume in vacuo and partitioned between brine (75ml) and ethyl acetate (2x200ml). Combined organic extracts were treated with saturated aqueous sodium bicarbonate (75ml) and brine (75ml), dried (sodium sulphate), concentrated in vacuo using high vacuum to remove DMF traces and purified by chromatography eluting with 0-15percent methanol/ dichloromethane. This gave tert-butyl (2JR)-2-[(4-benzylpiperazin-l-yl)carbonyl]piperazine-l-carboxylate as a white glass (5.0Ig).(2R)-l-(te/t-Butoxycarbonyl)-4-isopropylpiperazine-2-carboxyIic acid; To (22?)-l-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (500 mg) in dry methanol (10 mL) was added sodium cyanoborohydride (1.0 M in THF, 2.28 mL.) and the suspension was stirred for 18 h at 20 0C. The reaction was now in solution. The solvent was then removed under reduced pressure and was purified using eluent 10-70percent MeOH/DCM. After evaporation, the product was isolated as a white foam (513 mg), which was used without further purification.(2R)-l-(ter^-Butoxycarbonyl)-4-ethylpiperazine-2-carboxylic acid; To (2i?)-l-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1.406 g) and Na2CO3 (2.59 g) was added dry EtOH (28 ml) then ethyl iodide (0.54 ml) and the mixture heated at reflux for 18 h under argon. The solvent was then removed under reduced pressure and 5percentMeOH/DCM (40 ml) was added and stirred for 1 hour in a sealed flask. The solution was filtered and washed with dichloromethane (2 x 1OmL). The filtrate was then placed directly onto a 120g-silica cartridge and was purified using eluent 10-70percent MeOH/DCM. After evaporation, the product was isolated as a white foam (1.00 g), which was used without further purification.

Molecular Weight:230.26
XLogP3:-2.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:230.12665706
Monoisotopic Mass:230.12665706
Topological Polar Surface Area:78.9
Heavy Atom Count:16
Complexity:285
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes