Tolylboronic acid → Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate

HRID 1399608Notes

Reaction equation

HRID 1399608 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([CH3:17])[N:3]=1.B(O)(O)[C:19]1[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=1.C(N(C(C)C)CC)(C)C>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.COCCOC.O>[Cl:1][C:2]1[N:3]=[C:4]([CH3:17])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:6]([C:19]2[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=2)[N:7]=1

Participants

6

Reactant 3

HCID 79799Tolylboronic acidHCID 81531DiisopropylethylamineHCID 86665651HCID 86665651, compound

Product 1

HCID 86665647Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoateYield 39.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of mixture of methyl 2-(2,4-dichloro-6-methylpyrimidin-5-yl)pentanoate (2.56 g, 7.18 mmol) in a degassed mixture of 1,2-dimethoxyethane-water (3:1, 60 mL) were added p-tolylboronic acid (1.51 g; 10.77 mmol), tetrakis(triphenylphosphine)palladium (0.846 g; 0.732 mmol) and diisopropylethylamine (5 mL; 28.70 mmol). The resulting mixture was heated at 90° C. for 2 h. After cooling, the reaction mixture was partitioned between brine and ethyl acetate, the phases were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (3-20%) in heptane furnished 0.935 g (27%) of the title compound as an oil.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between brine and ethyl acetate
  3. customthe phases were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic extracts were dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (3-20%) in heptane

Sources & evidence

ORD record
ord-5a9cc3537c2f47e681d60c9c516523d7
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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