2,4-Dichloro-5-iodopyrimidine → 2,4-Dichloro-5-(2-(methylthio)phenyl)pyrimidine

HRID 711394Notes

Reaction equation

HRID 711394 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5](I)=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[S:24][CH3:25])O1>C1COCC1.O.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>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[S:24][CH3:25])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 2634382,4-Dichloro-5-iodopyrimidineHCID 177502722-Methylsulfanylphenylboronic acid, pinacol ester

Product 1

HCID 1183403012,4-Dichloro-5-(2-(methylthio)phenyl)pyrimidineYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 2,4-dichloro-5-iodopyrimidine (50.15 g, 182 mmol), 4,4,5,5-tetramethyl-2-(2-(methylthio)phenyl)-1,3,2-dioxaborolane (47.9 g, 192 mmol) in THF (1368 ml) and water (456 ml) was degassed with nitrogen. Pd(PPh3)4 (10.54 g, 9.12 mmol) was added and degassing continued for several minutes. The mixture was then heated to reflux at 70° C. overnight. After 24 hrs the reaction was cooled to room temperature, the aqueous layer was removed, and the organic layer was washed with brine. The aqueous layer was extracted once with EtOAc, and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography in 10-15% DCM 1-2% EtOAc/heptanes (v/v/v). The product was further purified by dissolving in EtOH and precipitating with heptanes, yielding 35.5 g (72% yield) of 2,4-dichloro-5-(2-(methylthio)phenyl)pyrimidine as white solids.

Workup

  1. customdegassing
  2. waitcontinued for several minutes
  3. temperatureThe mixture was then heated
  4. temperatureAfter 24 hrs the reaction was cooled to room temperature
  5. customthe aqueous layer was removed
  6. washthe organic layer was washed with brine
  7. extractionThe aqueous layer was extracted once with EtOAc
  8. dry with materialthe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by column chromatography in 10-15% DCM 1-2% EtOAc/heptanes (v/v/v)
  12. customThe product was further purified
  13. dissolutionby dissolving in EtOH
  14. customprecipitating with heptanes

Sources & evidence

ORD record
ord-f63d2c3d911d416ab78de4acf11420cc
Source dataset
uspto-grants-2015_11
Patent number
US09181270B2

Reaction notes

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