2-Chloroethyl chloroformate → HCID 58730268, compound

2-chloroethyl chloroformate (429 mg, 3 mmol) was added slowly to a mixture of tert-butyl 1-piperazinecarboxylate obtained as step (ii) in Example 2 (559 mg, 3 mmol) and diisopropylethylamine (407 mg, 3.15 mmol) in CHCl3 (25 ml) at 0° C. The mixture was stirred for 2 h at room temperature. CHCl3 (50 ml) was then added and the solution was washed with 5% NaHCO3 (3×50 ml), brine (2×50 ml), and then dried over Na2SO4. The solution was filtered and evaporated to dryness. The residue was dissolved in CH2Cl2 (25 ml) at room temperature, and propargylamine (0.205 ml, 165 mg, 3 mmol) was added. After 24 h of stirring at room temperature, the solvent was removed by vacuum, and to the residue was added 20 ml of a solution of TFA:H2O:TES:thioanisole (85:5:5:5). The mixture was then stirred at room temperature for 2 h. The solution was evaporated to dryness in vacuum. The resulted residue was dissolved in water (10 ml) and then basified with Na2CO3 (pH 11), and extracted with Et2OAc (3×50 ml). The organic layer was washed with brine (2×50 ml) and dried over Na2SO4 overnight. Evaporation in vacuum gave the title compound H1: (251 mg, 40% total yield). H1 NMR (250 MHz, CDCl3+D2O) 2.26 (m, 1H), 3.11 (s 2H), 3.29 (dd, J=10.21, 7.45 Hz, 2H), 4.29 (d, J=11.23, 7.12 Hz, 2H), 2.55 (dd, J=4.73, 4.50 Hz, 4H), 2.93 (dd, J=4.96, 4.84 Hz, 4H). Mass spectrometry: calculated for C10HnN3O2 m/z [M+H]+=212.26. found [M+H]+=212.22.

1. washthe solution was washed with 5% NaHCO3 (3×50 ml), brine (2×50 ml)
2. dry with materialdried over Na2SO4
3. filtrationThe solution was filtered
4. customevaporated to dryness
5. dissolutionThe residue was dissolved in CH2Cl2 (25 ml) at room temperature
6. stirringAfter 24 h of stirring at room temperature
7. customthe solvent was removed by vacuum
8. additionto the residue was added 20 ml of a solution of TFA
9. stirringThe mixture was then stirred at room temperature for 2 h
10. customThe solution was evaporated to dryness in vacuum
11. dissolutionThe resulted residue was dissolved in water (10 ml)
12. extractionextracted with Et2OAc (3×50 ml)
13. washThe organic layer was washed with brine (2×50 ml)
14. dry with materialdried over Na2SO4 overnight
15. customEvaporation in vacuum

ORD record

ord-06d21504af19440bb257aaefc6bd6492

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08685955B2