Ethyl Acetate → Tert-butyl 4-[2-chloro-4-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate

HRID 856105Notes

Reaction equation

HRID 856105 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:27]=[CH:26][C:18]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)=[CH:17][C:16]=1[Cl:28].CC(C)([O-])C.[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.O>[Cl:28][C:16]1[CH:17]=[C:18]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH:26]=[CH:27][C:15]=1[N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 230814412-(4-Bromo-3-chlorophenoxy)tetrahydropyranHCID 23676156Sodium t-butoxide

Product 1

HCID 23081313Tert-butyl 4-[2-chloro-4-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylateYield 62%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of tert-butyl piperazine-1-carboxylate (3.94 g, 21.6 mmol), 2-(4-bromo-3-chlorophenoxy)tetrahydropyran (5.61 g, 19.2 mol), palladium acetate (86.4 mg, 0.39 mmol), BINAP (172 mg, 0.58 mmol) and sodium tert-butoxide (2.4 g, 25.0 mmol) in toluene (40 ml) was refluxed under a nitrogen atmosphere for 2 hours. Ethyl acetate and water were added to the reaction mixture, which was stirred for a while. The insoluble substances were removed by filtration through Celite, and the filtrate was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1) to afford tert-butyl 4-[2-chloro-4-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate (4.72 g, yield 62%) as a yellow oil.

Workup

  1. temperaturewas refluxed under a nitrogen atmosphere for 2 hours
  2. customThe insoluble substances were removed by filtration through Celite
  3. extractionthe filtrate was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-ccc17aa4ba114fc2ae9b63c90c3381ed
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…