Piperidine → (2S)-2-(4-piperidin-1-yl-phenyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester

HRID 1091352Notes

Reaction equation

HRID 1091352 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21]1[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21]1[CH:26]=[CH:25][C:24]([N:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 8082PiperidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 53628944(S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl)piperazine

Product 1

HCID 66594922(2S)-2-(4-piperidin-1-yl-phenyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl esterYield 43%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (2S)-2-(4-bromophenyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester (1.06 g, 2.40 mmol), piperidine (0.29 ml, 2.88 mmol), palladium acetate (22.0 mg, 0.096 mmol), sodium tert-butoxide (323 mg, 3.36 mmol) and 2-(di-t-butylphosphino)biphenyl (57.0 mg, 0.192 mmol) in toluene (16 ml) was stirred at 80° C. for 6 hours. Water and ethyl acetate were added to the solution and the solution was passed through Celite column. The whole was extracted with ethyl acetate and the organic lawyer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give (2S)-2-(4-piperidin-1-yl-phenyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester (455 mg, 43%) as white crystals.

Workup

  1. extractionThe whole was extracted with ethyl acetate
  2. washthe organic lawyer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-124d30efdfcc466abbd130c98011a1ac
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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