Potassium Phosphate, Tribasic → Tert-butyl 4-(4-phenylpyrimidin-2-yl)piperazine-1-carboxylate

HRID 875005Notes

Reaction equation

HRID 875005 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([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:3]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[C:21]1([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[N:3]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 46738270tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate

Product 1

HCID 68577436Tert-butyl 4-(4-phenylpyrimidin-2-yl)piperazine-1-carboxylateYield 73.4%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate (300 mg, 1.0 mmol) and phenylboronic acid (183 mg, 1.5 mmol) were dissolved in toluene (10 mL) and the solution was purged with argon for 10 min. Potassium phosphate (426 mg, 2.0 mmol) was added to the reaction mixture, followed by a catalytic amount of Pd2(dba)3 (9 mg, 0.01 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (23 mg, 0.04 mmol). The reaction mixture was then heated to 115° C. for 10 h, 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 30% EtOAc in petroleum ether) to get tert-butyl 4-(4-phenylpyrimidin-2-yl)piperazine-1-carboxylate (250 mg, yield 73%). 1H NMR (300 MHz, MeOD) δ 8.28-8.23 (m, 3H), 7.46-7.43 (m, 3H), 7.34 (m, 1H), 3.80-3.77 (m, 4H), 3.56-3.53 (m, 4H), 1.48 (s, 9H). MS (ESI) m/z: Calculated for C19H24N4O2: 340.19. found: 341.2 (M+H)+

Workup

  1. customthe solution was purged with argon for 10 min
  2. temperaturecooled 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 30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-0c2d35e705de48c09bf052df294fbd2a
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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