Acetone → Tert-butyl 4-[2-tert-butyl-4-(1-hydroxy-1-methylethyl)phenyl]piperazine-1-carboxylate

HRID 534941Notes

Reaction equation

HRID 534941 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[C:9]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:8]=1.[CH3:30][C:31]([CH3:33])=[O:32].[Cl-].[NH4+]>C1COCC1>[C:26]([C:9]1[CH:8]=[C:7]([C:31]([OH:32])([CH3:33])[CH3:30])[CH:12]=[CH:11][C:10]=1[N:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 4

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 66751044Tert-butyl 4-(4-bromo-2-tert-butylphenyl)piperazine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 66751150Tert-butyl 4-[2-tert-butyl-4-(1-hydroxy-1-methylethyl)phenyl]piperazine-1-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of n-BuLi (1.6 M in n-hexane, 10.6 mL, 6.62 mmol) in THF (30 mL) was added a solution of tert-butyl 4-(4-bromo-2-tert-butylphenyl)piperazine-1-carboxylate (Example 85, 4.5 g, 11.3 mmol) in THF (15 mL) at −80° C. After stirred for 2 h at that temperature, it was added acetone (4 mL) and allowed to be warmed to room temperature. After 16 h, it was added saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and the solvent was evaporated under reduced pressure to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=98:2 to 80:20) to provide tert-butyl 4-[2-tert-butyl-4-(1-hydroxy-1-methylethyl)phenyl]piperazine-1-carboxylate (3.1 g, 73%) as a pale yellow solid.

Workup

  1. waitAfter 16 h
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customthe solvent was evaporated under reduced pressure
  6. customto give the crude product
  7. customThe product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=98:2 to 80:20)

Sources & evidence

ORD record
ord-48dc22f57bdd4e099c38bcb8871f7382
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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