Trifluoroacetic acid → HCID 67764603, compound

HRID 260905Notes

Reaction equation

HRID 260905 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([P:14]([CH2:18][CH3:19])([CH2:16][CH3:17])=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.[F:20][C:21]([F:26])([F:25])[C:22]([OH:24])=[O:23]>C(Cl)Cl>[F:20][C:21]([F:26])([F:25])[C:22]([OH:24])=[O:23].[CH2:16]([P:14]([N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)([CH2:18][CH3:19])=[O:15])[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 22400684HCID 22400684, compound

Product 1

HCID 67764603HCID 67764603, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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. customSolvent and trifluoroacetic acid were removed

Sources & evidence

ORD record
ord-4665dc36657b46b185e2987bee0ccca5
Source dataset
uspto-grants-1996_06
Patent number
US05530119

Reaction notes

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