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

HRID 1399559Notes

Reaction equation

HRID 1399559 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([CH3:14])[N:3]=1.COCCOC.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=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:6]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:7]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 66827Phenylboronic 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 66.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

To a suspension of methyl 2-(2,4-dichloro-6-methylpyrimidin-5-yl)acetate (4.42 g; 18.80 mmol) in a mixture of degassed DME (75 mL) and water (25 mL) was added phenyl boronic acid (5.73 g; 47 mmol), Tetrakis(triphenylphosphine) palladium(0) (2 g; 1.731 mmol) and diisopropyl ethylamine (12.96 mL; 75 mmol). The reaction was stirred under reflux for 3.5 h. The reaction mixture was 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 over 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 3.44 g (65%) of the title compound as a white solid. ESI/APCI(+): 277 (M+H).

Workup

  1. temperatureunder reflux for 3.5 h
  2. customThe reaction mixture was 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 over 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-a6d5a5b1e1ea46c59d108181722b0863
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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