Sodium Carbonate → tert-Butyl 4-(4-(5-chloro-2-hydroxyphenyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 46374

Reaction equation

HRID 46374 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4](I)[CH:3]=1.CC1(C)C(C)(C)OB([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)[CH:19]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.[Cl-].[NH4+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)[CH:19]=2)[CH:3]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 312751,4-DioxaneHCID 6202344-Chloro-2-iodophenolHCID 179989162-(4-tert-Butoxycarbonylpiperazin-1-yl)pyridine-4-boronic acid, pinacol ester

Product 1

HCID 136063613tert-Butyl 4-(4-(5-chloro-2-hydroxyphenyl)pyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-2-iodophenol (367 mg, 1.44 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate (707.5 mg, 1.817 mmol), and sodium carbonate (615.0 mg, 5.802 mmol) in 1,4-dioxane (6.0 mL, 77 mmol) and water (2.0 mL, 110 mmol) was sparged 5 minutes with argon. Tetrakis(triphenylphosphine)palladium(0) (100.0 mg, 0.08654 mmol) was added, the vial was capped, and the reaction mixture was heated at 90° C. After 4 hours, the reaction mixture was cooled to ambient temperature and poured into water. Saturated aqueous ammonium chloride was added, and the mixture was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated onto diatomaceous earth. The residue was purified by automated flash chromatography (24 g SiO2, hexanes to ethyl acetate) to afford the product as an amber oil that solidified on standing (491 mg, 74%).

Workup

  1. customwas sparged 5 minutes with argon
  2. customthe vial was capped
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. extractionthe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated onto diatomaceous earth
  9. customThe residue was purified by automated flash chromatography (24 g SiO2, hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-14704b945236434ca4388743492434e8
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Linked notes

Loading…