1-Piperazinecarboxylic acid, 4,4'-(1,3-propanediyl)bis-, 1,1'-bis(1,1-dimethylethyl) ester synthesis

Yield:1279815-19-8 78%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 20; for 24 h;

Steps:

Di-tert-butyl 4,4'-(propane-1,3-diyl)bis(piperazine-1-carboxylate) 10

To a stirred solution of 300 mg (1.61 mmol) of mono Boc-piperazine 6 in 5 mL of dry DMF were added 82.0 μL (163 mg, 0.80 mmol) of 1,3-dibromopropane 8 and 890 mg (6.44 mmol) of K₂CO₃ at room temperature.
After 24 h, reaction mixture was diluted with 25 mL of water and extracted with two 50 mL portions of ethyl acetate.
The organic phase was dried (MgSO₄) and concentrated under diminished pressure.
The residue was purified by chromatography on a silica gel column (10*2 cm).
Elution with 19:1 ethyl acetate/methanol gave desired product 10 as a colorless solid: yield 521 g (78%); silica gel TLC R_f 0.27 (9:1 ethyl acetate/methanol); ¹H NMR (CDCl₃) δ 1.46 (s, 18H), 1.64-1.74 (m, 2H), 2.35-2.39 (m, 12H) and 3.41-3.44 (m, 8H); ¹³C NMR (CDCl₃) δ 28.4, 31.4, 36.4, 53.1, 56.6, 79.5 and 154.7.

References:

US2019/106396,2019,A1 Location in patent:Paragraph 0040; 0041; 0047