1,2-Dimethoxyethane → Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)acetate

HRID 1399561Notes

Reaction equation

HRID 1399561 reaction equation
[Cl:1][C:2]1[N:7]=C(Cl)[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([CH3:14])[N:3]=1.COCCOC.B(O)(O)[C:22]1[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=1.C(N(C(C)C)CC)(C)C>[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.O>[Cl:1][C:2]1[N:3]=[C:4]([CH3:14])[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:28]([C:25]2[CH:24]=[CH:23][CH:22]=[CH:27][CH:26]=2)[N:7]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 79799Tolylboronic acidHCID 81531DiisopropylethylamineHCID 19044674Methyl 2-(2,4-dichloro-6-methylpyrimidin-5-yl)acetate

Product 1

HCID 86665645Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)acetateYield 81.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

To a suspension of methyl 2-(2,4-dichloro-6-methylpyrimidin-5-yl)acetate (4 g; 17.02 mmol) in a mixture of degassed DME (75 mL) and water (25 mL) was added p-tolylboronic acid (4.63 g; 34 mmol), Tetrakis(triphenylphosphine) palladium(0) (2 g; 1.731 mmol) and diisopropyl ethylamine (11.73 mL; 68.1 mmol). The reaction was stirred under reflux for 3.5 h. The reaction mixture was then partitioned between brine and ethyl acetate. The phases were separated and the water layer was extracted with ethyl acetate. The combined organic layers were dried with magnesium sulphate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (5-40%) in heptane to give 3.82 g (61%) of the title compound as a white solid (purity: 80%). ESI/APCI(+): 291 (M+H).

Workup

  1. temperatureunder reflux for 3.5 h
  2. customThe reaction mixture was then partitioned between brine and ethyl acetate
  3. customThe phases were separated
  4. extractionthe water layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried with magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (5-40%) in heptane

Sources & evidence

ORD record
ord-ed14b3a07a9544b097d214f1dd3b5c38
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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