5-Bromopyrimidine → tert-Butyl 4-(pyrimidin-5-yl)piperazine-1-carboxylate

HRID 875000Notes

Reaction equation

HRID 875000 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[N:4]1[CH:3]=[C:2]([N:18]2[CH2:17][CH2:16][N:15]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:20][CH2:19]2)[CH:7]=[N:6][CH:5]=1

Participants

7

Reactant 3

HCID 783445-BromopyrimidineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 67325143tert-Butyl 4-(pyrimidin-5-yl)piperazine-1-carboxylateYield 42.2%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

5-Bromo pyrimidine (1.0 g, 6.29 mmol) and 1-Boc-piperazine (1.17 g, 6.28 mmol) were dissolved in toluene (20 mL) and the solution was purged with argon for 10 min. Sodium tert-butoxide (816 mg, 8.49 mmol) and catalytic Pd(PtBu3)2 (320 mg, 0.63 mmol) were added and the reaction mixture was heated to 120° C. for 10 h. The reaction mixture was cooled to room temperature, diluted with EtOAc and filtered through Celite. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 80% EtOAc in petroleum ether) to get tert-butyl 4-(pyrimidin-5-yl)piperazine-1-carboxylate (700 mg, yield 42%). 1H NMR (300 MHz, MeOD) δ 8.57 (s, 1H), 8.48 (m, 2H), 3.61-3.58 (m, 4H), 3.30-3.27 (m, 4H), 1.47 (s, 9H). MS (ESI) m/z: Calculated for C13H20N4O2: 264.16. found: 265.0 (M+H)+

Workup

  1. customthe solution was purged with argon for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through Celite
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 80% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-22b7ab31a6434ab7aba73a57804f88a6
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

Loading…