Dichloromethane → Methyl 2-(4-benzyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoate

HRID 1399683Notes

Reaction equation

HRID 1399683 reaction equation
[CH2:1]([Mg]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:11]1[C:16]([CH:17]([CH2:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:15]([CH3:25])[N:14]=[C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:12]=1.ClCCl.C([Zn])C1C=CC=CC=1>O1CCCC1.O.[Cl-].[Zn+2].[Cl-]>[CH2:1]([C:11]1[C:16]([CH:17]([CH2:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:15]([CH3:25])[N:14]=[C:13]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 86665652Methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoateHCID 178418336HCID 178418336, compoundHCID 178528066HCID 178528066, compound

Product 1

HCID 50994995Methyl 2-(4-benzyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoateYield 81%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C.) solution of anhydrous zinc chloride (0.060 mg; 0.439 mmol) in tetrahydrofuran (0.8 mL) under nitrogen atmosphere was added dropwise a benzylmagnesium chloride solution (1M in THF) (0.408 mL; 0.408 mmol). After 15 min, the solution was allowed to warm up to room temperature for 10 min. To an argon purged reaction tube was added methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoate (0.100 g; 0.314 mmol), (1,1′-Bis(diphenylphosphino)ferrocene)-dichloropalladium(II) complex with dichloromethane (0.015 g; 0.022 mmol) and tetrahydrofuran (3 mL). The milky benzylzinc solution was added dropwise, the mixture was stirred at room temperature for 30 min and then heated at 65° C. for 20 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The combined organics were washed with a solution of ethylenediaminetetraacetic acid, water, brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane furnished 0.095 g (81%) of the title compound as a colorless oil.

Workup

  1. customTo an argon purged
  2. customreaction tube
  3. temperatureheated at 65° C. for 20 h
  4. extractionextracted twice with ethyl acetate
  5. washThe combined organics were washed with a solution of ethylenediaminetetraacetic acid, water, brine
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane

Sources & evidence

ORD record
ord-789809e2357a4717ac63d8427475968c
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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