Piperazine → HCID 18436716, compound

HRID 456455Notes

Reaction equation

HRID 456455 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2Br)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH:1]([N:14]1[CH2:17][CH:16]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 17952544HCID 17952544, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 18436716HCID 18436716, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-Benzhydryl-3-(2-bromo-phenoxy)-azetidine (3.6 g, 9.16 mmol), piperazine (946 mg, 11 mmol), BINAP (427 mg, 1.38 mmol), Pd2dba3 (410 mg, 0.46 mmol) and sodium tert-butoxide (1.23 g, 12.8 mmol) were dissolved into toluene (100 mL). The solution was degassed under vacuum and bubbled with nitrogen. The vessel was sealed under nitrogen and heated to 90° C. for about 24 hours. Diethyl ether (500 ml) was added, and the solution was filtered through a bed of celite. The solution was concentrated to an orange oil. Purification by silica gel chromatography [1% NH3 in methanol/ethyl acetate (1 L), 5% NH3 in methanol/ethyl acetate (1 L), and 10% NH3 in methanol/ethyl acetate (1L)] gave the title compound as an orange powder (2.0 g, 65%).

Workup

  1. customThe solution was degassed under vacuum
  2. custombubbled with nitrogen
  3. customThe vessel was sealed under nitrogen
  4. additionDiethyl ether (500 ml) was added
  5. filtrationthe solution was filtered through a bed of celite
  6. concentrationThe solution was concentrated to an orange oil
  7. customPurification by silica gel chromatography [1% NH3 in methanol/ethyl acetate (1 L), 5% NH3 in methanol/ethyl acetate (1 L), and 10% NH3 in methanol/ethyl acetate (1L)]

Sources & evidence

ORD record
ord-fd2fe9c61d5043b4a021616bf0fe751b
Source dataset
uspto-grants-2007_03
Patent number
US07186715B2

Reaction notes

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