Potassium Phosphate, Tribasic → Methyl 5-{4-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperazin-1-yl}pyridine-2-carboxylate

HRID 1021227Notes

Reaction equation

HRID 1021227 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[C:11]([F:22])=[C:12]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[C:24]1[CH:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Si:1]([O:8][CH2:9][C:10]1[C:11]([F:22])=[C:12]([N:16]2[CH2:21][CH2:20][N:19]([C:24]3[CH:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=3)[CH2:18][CH2:17]2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 7016458Methyl 5-bromopyridine-2-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866862021-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperazine

Product 1

HCID 86686201Methyl 5-{4-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperazin-1-yl}pyridine-2-carboxylateYield 43.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperazine (500 mg) was mixed with dioxane (15 ml), and methyl 5-bromopyridine-2-carboxylate (399 mg), palladium acetate (35 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (147 mg), and potassium phosphate (981 mg) were added thereto, followed by stirring at 100° C. for 48 hours. The reaction mixture was cooled to room temperature, and filtered by the addition of CHCl3 and Celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/hexane) to obtain methyl 5-{4-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperazin-1-yl}pyridine-2-carboxylate (310 mg).

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered by the addition of CHCl3 and Celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (EtOAc/hexane)

Sources & evidence

ORD record
ord-3d38322a3ca44e0abadd2aa2816f94e6
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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