P-Cresol → Tert-butyl 4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazine-1-carboxylate

HRID 1023328Notes

Reaction equation

HRID 1023328 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:23]=[CH:22][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[CH:24]1[C:29](O)=[CH:28][CH:27]=[C:26]([CH3:31])[CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1.C1COCC1>[CH3:31][C:26]1[CH:27]=[CH:28][C:29]([O:1][CH2:2][CH2:3][C:4]2[CH:5]=[CH:6][C:7]([CH2:8][N:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:11][CH2:10]3)=[CH:22][CH:23]=2)=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 2879P-CresolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 67328866Tert-butyl 4-[4-(2-hydroxyethyl)benzyl]piperazine-1-carboxylate

Product 1

HCID 67328194Tert-butyl 4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazine-1-carboxylateYield 63.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a THF (40 mL) solution of tert-butyl 4-[4-(2-hydroxyethyl)benzyl]piperazine-1-carboxylate (4.74 g) and p-cresol (1.76 g) were added triphenylphosphine (4.27 g) and 2.2 M solution of DEAD in toluene (7.40 mL) at 0° C. After stirring at room temperature for 85 hours, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1 to 1/2), then the concentrated eluate was diluted with CH2Cl2, and washed with 5 M NaOH and saturated aqueous NaCl, dried over anhydrous MgSO4, and concentrated under reduced pressure to give tert-butyl 4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazine-1-carboxylate as a yellow solid (3.87 g).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1 to 1/2)
  3. additionthe concentrated eluate was diluted with CH2Cl2
  4. washwashed with 5 M NaOH and saturated aqueous NaCl
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-214170316db2489aab31079ad47c5f6b
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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