Potassium Carbonate → 3-[3-(6-Cyclopropyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

HRID 1767594Notes

Reaction equation

HRID 1767594 reaction equation
[C:1]([C:3]1[CH:4]=C(B(O)O)C=C[CH:8]=1)#N.Br[C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH2:21][CH2:20]2)=[N:17][CH:18]=1.Br[C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25]N=1.[Cl-].[CH:31]1([Zn+])[CH2:33][CH2:32]1.[C:35]([O-:38])(O)=[O:36].[Na+].C([O-])([O-])=[O:41].[K+].[K+]>C1COCC1.C1(C)C=CC=CC=1.CCO.O.CCOC(C)=O.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>[C:3]([O:38][C:35](=[O:36])[CH2:25][C:26]([C:27]1[CH:33]=[CH:31][CH:32]=[C:23]([C:13]2[CH:18]=[N:17][C:16]([CH:19]3[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[CH:28]=1)=[O:41])([CH3:4])([CH3:8])[CH3:1]

Participants

13

Reactant 6

HCID 11430Potassium CarbonateHCID 693532,5-DibromopyridineHCID 516892Sodium BicarbonateHCID 27343253-Cyanophenylboronic acidHCID 223177225-Bromo-2-cyclopropylpyridineHCID 178479835HCID 178479835, compound

Product 1

HCID 694893843-[3-(6-Cyclopropyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Compound K7 was obtained from 3-(6-cyclopropyl-pyridin-3-yl)-benzonitrile [prepared by the following procedure: A mixture of 3-cyanophenylboronic acid [CAS-No. 150255-96-2] (8.82 g, 60 mmol), crude 5-bromo-2-cyclopropylpyridine {prepared by the following procedure: A mixture of 2,5-dibromopyridine (11.85 g, 50 mmol), cyclopropyl zinc chloride (0.4 M in THF, 160 mL, 64 mmol), Pd(PPh3)4 (578 mg, 1 mol %) in THF (55 mL) was stirred under Argon atmosphere at 70° C. for 1.5 h. Cooled to RT, poured into sat. NaHCO3-solution, extracted with ether, washed with brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil (12.36 g).} (ca. 60 mmol), Pd(PPh3)4 (1.733 g, 3 mol %) and K2CO3 (13.82 g, 100 mmol) in toluene (250 mL), EtOH (22 mL) and H2O (50 mL) was stirred at 80° C. for 14 h. Cooled to RT, diluted with EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown solid, which was purified by silica gel column chromatography with cyclohexane/-EtOAc.] (9.88 g, 44.87 mmol) by treatment with tert-butyl bromoacetate and activated zinc, followed by hydrolysis with 10% HCl according to general procedure K (method d).

Workup

  1. customprepared by the following procedure
  2. customprepared by the following procedure
  3. temperatureCooled to RT
  4. extractionextracted with ether
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent in vacuum
  8. waitleft a brown oil (12.36 g)
  9. temperatureCooled to RT
  10. washwashed with sat. NaHCO3-solution and brine
  11. dry with materialdried over Na2SO4
  12. customRemoval of the solvent in vacuum
  13. waitleft a brown solid, which
  14. customwas purified by silica gel column chromatography with cyclohexane/-EtOAc
  15. custom] (9.88 g, 44.87 mmol) by treatment with tert-butyl bromoacetate and activated zinc, followed by hydrolysis with 10% HCl according to general procedure K (method d)

Sources & evidence

ORD record
ord-c7825db3a5d94716b1727c4a690217cc
Source dataset
uspto-grants-2007_06
Patent number
US07235547B2

Reaction notes

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