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

HRID 522675Notes

Reaction equation

HRID 522675 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.Cl>O1CCOCC1.C1COCC1.C(OCC)(=O)C.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

9

Reactant 4

HCID 313Hydrochloric AcidHCID 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 4

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 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) and triphenylphosphine (376 mg, 2.92 mmol) in dioxane (100 mL) was added tributyl(1-ethoxyvinyl)stannane (5.3 mL, 16.1 mL) under N2, 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 column chromatography to afford the title compound (3.0 g, 67%). MS (ES+) C15H22N4O3 requires: 306, found: 251 [M-56+H]+.

Workup

  1. temperatureThe reaction was cooled to RT
  2. stirringThe mixture was stirred at RT for 30 mins
  3. customThe organic phase was separated
  4. washwashed with water (3×100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5a7d06591f7f460d95e1aa0bff764555
Source dataset
uspto-grants-2016_05
Patent number
US09334263B2

Reaction notes

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