Potassium Carbonate → 4-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester

HRID 220445Notes

Reaction equation

HRID 220445 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15](Cl)=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[F:21])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 593218363-(4-BOC-piperazino)-2-chloropyridine

Product 1

HCID 687242774-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl esterYield 91%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve 4-(2-chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (0.9 g, 3.0 mmol) in a mixture of 5 mL 1,2 dimethoxyethane and 4 mL water. Add 2-fluorophenylboronic acid (0.51 g, 3.64 mmol) followed by tetrakis(triphenylphosphine) palladium(0) (0.35 g, 0.30 mmol), and potassium carbonate (1.13 g, 8.2 mmol). Heat the reaction mixture at 100° C. for 22 hr. Cool to room temperature, concentrate and partition the residue between ethyl acetate and water. Extract water layer with ethyl acetate. Wash combined organic layers with brine. Dry organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 10:90 to 30:70 ethyl acetate:hexanes), to give 4-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester (91%). MS (ES): m/z=358 [M+H]+.

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. custompartition the residue between ethyl acetate and water
  4. washWash
  5. filtrationDry organic extracts (sodium sulfate), filter
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 10:90 to 30:70 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-b6bf382244e44ddeae86586d903d0ba8
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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