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

HRID 1399568Notes

Reaction equation

HRID 1399568 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.[Br-].[CH2:24]([Zn+])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>[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.C1COCC1>[CH2:24]([C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 2

HCID 86665646Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)pentanoateHCID 178419772HCID 178419772, compound

Product 1

HCID 50996263Methyl 2-(2-benzyl-4-methyl-6-phenylpyrimidin-5-yl)pentanoateYield 64%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

THF (4 ml) was added to an argon purged glass tube (20 mL) containing methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)pentanoate (135 mg; 0.423 mmol) and tetrakis(triphenylphosphine) palladium(0) (24.47 mg; 0.021 mmol). The mixture was stirred at room temperature for 10 min and, after dissolution of the solids, benzylzinc bromide (1.694 ml; 0.847 mmol; 0,5 M in THF) was added dropwise. Stirring at room temperature was continued for 15 min followed by stirring at 60° C. for 8 h. The reaction was quenched by adding a saturated ammonium chloride solution. To this suspension was added a saturated disodium ethylenediamine tetraacetate solution and the mixture was stirred at room temperature for 15 min. The mixture was extracted twice with ethyl acetate and the organic layers were washed with brine and dried over magnesium sulphate. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane to give 101 mg (64%) of the title compound. ESI/APCI(+): 375 (M+H). ESI/APCI(−): 373 (M−H).

Workup

  1. additionwas added dropwise
  2. stirringStirring at room temperature
  3. waitwas continued for 15 min
  4. stirringby stirring at 60° C. for 8 h
  5. customThe reaction was quenched
  6. additionby adding a saturated ammonium chloride solution
  7. additionTo this suspension was added a saturated disodium ethylenediamine tetraacetate solution
  8. stirringthe mixture was stirred at room temperature for 15 min
  9. extractionThe mixture was extracted twice with ethyl acetate
  10. washthe organic layers were washed with brine
  11. dry with materialdried over magnesium sulphate
  12. customThe crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane

Sources & evidence

ORD record
ord-5a99ffb632014786b0380e09f3992089
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

Loading…