Triethylamine → HCID 22400684, compound

HRID 260904Notes

Reaction equation

HRID 260904 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N([CH2:19][CH3:20])CC)C.C([O:23][P:24](Cl)(OCC)=O)C.[CH2:30]1[CH2:34]OCC1.O>CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([P:24]([CH2:19][CH3:20])([CH2:34][CH3:30])=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 13139Diethyl chlorophosphateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 21881883Oxolane--water (1/1)

Product 1

HCID 22400684HCID 22400684, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butyloxycarbonylpiperazine (1.0 g, 5.34 mmol) was dissolved in 5 mL of THF:water (1:1) and cooled in an ice bath. Triethylamine (1.45 mL, 10.68 mmol), followed by diethylchlorophosphate (1.16 mL, 8.01 mmol) in 5 mL of ether were added, and stirred at 0° C. for 1 hour and at room temperature for 2 hours. Solvents were removed and 40 mL of ethyl acetate was added to the residue. The ethyl acetate layer was washed with brine (30 mL×3) and dried over anhydrous sodium sulfate. After filtered, the filtrate was concentrated in vacuo to yield 1.5 g of N-tert-butyloxycarbonyl-N'-diethylphosphoryl-piperazine in 88% yield as an oil. MS m/z M+H=323, M+NH4 =340. H1 -NMR (in CDCl3) δ=1.32 (t, 6H, 2×CH3), 1.48 (s, 9H, Boc), 3.1 (m, 4H, piperazine), 3.37 (t, 4H, piperazine), 4.05 (m, 4H, 2×OCH2). The obtained N-tert-butyloxycarbonyl-N'-diethylphosphoryl-piperazine (1.5 g, 4.66 mmol) was dissolved in 10 mL of 10% trifluoroacetic acid in methylene chloride and stirred at room temperature for 30 minutes. Solvent and trifluoroacetic acid were removed to obtain 1.6 g of N-diethylphosphorylpiperazine trifluoroacetic acid salt in quantitative yield. MS m/z M+H=223, H1 -NMR (in MeOH-d4) δ=1.35 (m, 6H, 2×CH3), 3.19 (m, 4H, piperazine) (m, 4H, piperazine), 4.05 (m, 4H, 2×OCH2). Following the procedure of Example 6, but replacing 1-benzylpiperazine with 1-diethylphosphorylpiperazine, provides the desired compound. The product of Example 3 (2.1 g, 2.03 mmol), base-treated salt free form of N-diethylphosphorylpiperazine (1.358 g, 6.09 mmol), and triethylamine (0.85 mL, 6.09 mmol) in 10 mL of methylene chloride are used. The obtained product (1.0 g) is treated with 48%-HF (4 mL) in 35 mL of acetonitrile in the procedure described in Example 5 to yield the pure title compound.

Workup

  1. temperaturecooled in an ice bath
  2. additionwere added
  3. customSolvents were removed
  4. addition40 mL of ethyl acetate was added to the residue
  5. washThe ethyl acetate layer was washed with brine (30 mL×3)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtered
  8. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-0afb43ad512e4979b1f6a85c794d0c59
Source dataset
uspto-grants-1996_06
Patent number
US05530119

Reaction notes

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