(S)-1,3-dibenzylpiperazine → HCID 66582509, compound

HRID 1972502Notes

Reaction equation

HRID 1972502 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][C@@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([C:28]([OH:34])([CH3:33])[C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:14]([C@H:10]1[CH2:9][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:12][N:11]1[C:22]1[CH:27]=[CH:26][C:25]([C:28]([OH:34])([CH3:33])[C:29]([F:31])([F:32])[F:30])=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 10825673(S)-1,3-dibenzylpiperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 583472902-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol

Product 1

HCID 66582509HCID 66582509, compoundYield 33.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a sealable vial (S)-1,3-dibenzylpiperazine (0.617 g, 2.316 mmol, Alfa Aeser, Ward Hill, Mass.), 2-(4-bromophenyl)-1,1,1-trifluoropropan-2-ol (0.623 g, 2.316 mmol, Example 27, Step 1), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (0.071 g, 0.058 mmol, Strem Chemicals, Newburyport, Mass.), Pd2(dba)3 (0.067 g, 0.116 mmol, Strem Chemicals, Newburyport, Mass.), and sodium tert-butoxide (0.556 g, 5.79 mmol) were combined and suspended in toluene (5 mL). The vial was purged with N2 for 5 min and was then heated at 100° C. for 15 h. The mixture was diluted with EtOAc (20 mL), the layers were separated and the organics were washed with water (10 mL) and brine (10 mL). The organic extracts were dried over MgSO4, filtered, and concentrated. The crude material was absorbed onto silica gel and purified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes) to give 2-(4-((2S)-2,4-dibenzyl-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.355 g).

Workup

  1. customThe vial was purged with N2 for 5 min
  2. additionThe mixture was diluted with EtOAc (20 mL)
  3. customthe layers were separated
  4. washthe organics were washed with water (10 mL) and brine (10 mL)
  5. dry with materialThe organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto silica gel
  9. custompurified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5005f83411c546399c87723b8b01a3f6
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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