Triphenylphosphine → Tert-butyl 4-(5-acetylpyrimidin-2-yl)piperazine-1-carboxylate

HRID 1498852Notes

Reaction equation

HRID 1498852 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([Sn](CCCC)(CCCC)[C:45]([O:47]CC)=[CH2:46])CCC>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:45]([C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1)(=[O:47])[CH3:46]

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate

Product 1

HCID 118023389Tert-butyl 4-(5-acetylpyrimidin-2-yl)piperazine-1-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (5.0 g, 14.6 mmol), palladium diacetate (240 mg, 1.46 mmol), triphenylphosphine (376 mg, 2.92 mmol) and tributyl(1-ethoxyvinyl)stannane (5.3 mL, 16.1 mL) in dioxane (100 mL) was degassed with nitrogen for three times, and the reaction mixture was stirred at 80° C. overnight. The reaction was cooled to RT and diluted with THF (100 mL), followed by the addition of 2 N HCl (100 mL). The mixture was stirred at RT for 30 mins, and LCMS showed the reaction was completed. The reaction mixture was diluted with ethyl acetate (200 mL). The organic phase was separated, washed with water (3×100 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography to afford the title compound (3.0 g, 67%). MS (ES+) C15H22N4O3 requires: 306. found: 251 [M−56+H]+.

Workup

  1. customwas degassed with nitrogen for three times
  2. temperatureThe reaction was cooled to RT
  3. additiondiluted with THF (100 mL)
  4. additionfollowed by the addition of 2 N HCl (100 mL)
  5. stirringThe mixture was stirred at RT for 30 mins
  6. additionThe reaction mixture was diluted with ethyl acetate (200 mL)
  7. customThe organic phase was separated
  8. washwashed with water (3×100 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6417f878f5f84509b323c14be1202831
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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