tert-Butyl piperazine-1-carboxylate → HCID 63701856, compound

Temperature

80 °C

3,4-Epoxypyrrolidine carbamate Wang resin (0.15 g, 0.18 mmol) was placed in a glass reaction vessel (4 mL). LiClO4 (57 mg, 3 eq.), N-Boc piperazine (186 mg, 5.5 eq.) and acetonitrile (2 mL) were added. The glass reactor was closed with a screw cap and the reaction mixture was heated at 80° C. for 43 h. The resin was transferred into syringes and washed with acetonitrile:H2O (1:1, 2×), DMF (3×), MeOH (3×), DMF (3×), and CH2Cl2 (5×). The BOC group was removed by treating the resin with 10% methyl sulfide in TFA (2 mL) for 1 hour. This solution was saved and later combined with a cleavage solution. The product was further cleaved from resin by shaking with a solution of TFA:CH2Cl2:H2O (2 mL of 70:30:1.5) for 2.5 h (2×). All the solutions were combined and condensed to afford 170 mg of crude 4-piperazin-1-yl-pyrrolidin-3-ol (bistrifluoroacetate salt, used without purification). The crude 4-piperazin-1-yl-pyrrolidin-3-ol was dissolved in DMF (dry, 2 mL). To this solution was added 4-chloro-benzoyl chloride (46L, 0.36 mmol), diisopropyl ethyl amine (620 μL, 3.6 mmol), and DMAP (2 mg). The solution was stirred at RT for 30 minutes, and then separated by preparative LC-MS to yield 16 mg of the title compound as the trifluoroacetate salt. ESIMS ([M+H]+): 448.3 (100).

1. customThe glass reactor was closed with a screw
2. customcap
3. washwashed with acetonitrile:H2O (1:1, 2×), DMF (3×), MeOH (3×), DMF (3×), and CH2Cl2 (5×)
4. customThe BOC group was removed
5. additionby treating the resin with 10% methyl sulfide in TFA (2 mL) for 1 hour
6. customcondensed

ORD record

ord-86bb45664cd143e68673f123c23e6af5

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399455B2