Triphenylphosphine → 4-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1020029

Reaction equation

HRID 1020029 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:27]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1B(O)O)[CH3:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[O:29][CH2:27][CH3:28])[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 2734902(2-Ethoxyphenyl)boronic acidHCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 595090544-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl esterYield 50.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred mixture of 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (6.15 g, 16.4 mmol), 2-ethoxyphenylboronic acid (II) (3.00 g, 18.1 mmol) in saturated sodium carbonate solution (10 ml) and 1,4-dioxane (10 ml) was added palladium(II) acetate (0.81 g, 3.6 mmol) followed by triphenylphosphine (0.94 g, 3.6 mmol) at room temperature under an atmosphere of nitrogen. The resulting reaction mixture was heated to reflux at 110° C. for one hour and monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3×100 ml). The organic layers were separated, combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, elution with 50% ethyl acetate/n-hexanes) to afford 4-[6-(2-ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (IX) (3.8 g, 50%) as a pale yellow oil.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. filtrationThe reaction mixture was filtered through a celite bed
  4. extractionthe filtrate was extracted with ethyl acetate (3×100 ml)
  5. customThe organic layers were separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash column chromatography (silica gel, elution with 50% ethyl acetate/n-hexanes)

Sources & evidence

ORD record
ord-a09d0351fa4c4c23a4960450448628ec
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Linked notes

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