Trifluoroacetic acid → HCID 67764465, compound

HRID 260907Notes

Reaction equation

HRID 260907 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.[F:22][C:23]([F:28])([F:27])[C:24]([OH:26])=[O:25]>C(Cl)Cl>[F:22][C:23]([F:28])([F:27])[C:24]([OH:26])=[O:25].[O:19]1[CH2:20][CH2:21][N:16]([C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[O:15])[CH2:17][CH2:18]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 100176291,1-Dimethylethyl 4-(4-morpholinylcarbonyl)-1-piperazinecarboxylate

Product 1

HCID 67764465HCID 67764465, 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 4-morpholinocarbonyl chloride (0.752 mL, 6.4 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 1.39 g of N-tert-butyloxycarbonyl-N'-morpholinocarbonyl-piperazine in 87% yield as a solid. MS m/z M+H=300, M+NH4 =317; H1 -NMR (in CDCl3) δ=1.49 (s, 9H, Boc), 3.25 (m, 8H, 4×CH2), 3.52 (m, 4H), 3.65 (m, 4 H). The obtained N-tert-butyloxycarbonyl-N'-morpholinocarbonyl-piperazine (1.38 g, 4.62 mmol) was dissolved in 10 mL of 20% trifluoroacetic acid in methylene chloride and stirred at room temperature for 1 hour. Solvent and trifluoro acetic acid were removed to obtain N-morpholinocarbonylpiperazine trifluoroacetic acid salt in quantitative yield. MS m/z M+H=200, H1 -NMR (in MeOH-d4) δ=3.22 (m, 4H), 3.3 (m, 4H), 3.45 (m, 4H), 3.65 (m, 4H). The obtained N-morpholinocarbonylpiperazine trifluoroacetic acid salt is dissolved in 30 mL of acetonitrile and cooled in an ice bath. Solid sodium bicarbonate is added to the acetonitrile solution and stirred for an additional 2 hours. Solid is filtered off and the filtrate is concentrated in vacuo to yield N-morpholinocarbonylpiperazine. Following the procedure of Example 6, but replacing 1-benzylpiperazine with 1-morpholinocarbonylpiperazine, provides the desired compound. The product of Example 3 (2.1 g, 2.03 mmol), 1-morpholinocarbonylpiperazine (1.212 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 trifluoro acetic acid were removed

Sources & evidence

ORD record
ord-3bb39ef356124f4d88f8c463da15596b
Source dataset
uspto-grants-1996_06
Patent number
US05530119

Reaction notes

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