Toluene → Tert-butyl4-{4-[1-(tert-butoxycarbonyl)cyclopropyl]phenyl}piperazine-1-carboxylate

HRID 557885Notes

Reaction equation

HRID 557885 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[N:18]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.CCC([O-])(C)C.[Na+].ClCCl.C1(C)C=CC=CC=1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:14]([O:13][C:11]([C:8]1([C:5]2[CH:6]=[CH:7][C:2]([N:21]3[CH2:20][CH2:19][N:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22]3)=[CH:3][CH:4]=2)[CH2:10][CH2:9]1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 5

HCID 1140TolueneHCID 6344DichloromethaneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733478Sodium 2-methylbutan-2-olateHCID 66661920Tert-butyl 1-(4-bromophenyl)cyclopropanecarboxylate

Product 1

HCID 66662612Tert-butyl4-{4-[1-(tert-butoxycarbonyl)cyclopropyl]phenyl}piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 1-(4-bromophenyl)cyclopropanecarboxylate (297.2 mg, 0.001000 mol), tert-butyl piperazine-1-carboxylate (186.2 mg, 0.001000 mol), sodium tert-pentoxide (110.1 mg, 0.001000 mol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (1:1) (24.5 mg, 0.0000300 mol) and 1,1′ bis(diphenylphosphino)ferrocene (16.6 mg, 0.0000300 mol) was deaerated and then charged with nitrogen. To the mixture was added toluene (3.0 mL, 0.028 mol), and the resulting mixture was heated at 100° C. overnight. The mixture was poured into ice-water and was extracted with ethyl acetate (4×10 mL). The combined organic layer was washed with water and brine successively, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Combiflash with ethyl acetate/hexane.

Workup

  1. additioncharged with nitrogen
  2. extractionwas extracted with ethyl acetate (4×10 mL)
  3. washThe combined organic layer was washed with water and brine successively
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by Combiflash with ethyl acetate/hexane

Sources & evidence

ORD record
ord-29ed456419a944858500276650aa9f0b
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Reaction notes

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