2-METHYLSULFANYLPHENYLBORONIC ACID, PINACOL ESTER

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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. degassing continued for several minutes The mixture was then heated After 24 hrs the reaction was cooled to room temperature the aqueous layer was removed the organic layer was washed with brine The aqueous layer was extracted once with EtOAc the combined organic layers were dried over sodium sulfate filtered 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 precipitating with heptanes

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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. degassing continued for several minutes The mixture was then heated After 24 hrs the reaction was cooled to room temperature the aqueous layer was removed the organic layer was washed with brine The aqueous layer was extracted once with EtOAc the combined organic layers were dried over sodium sulfate filtered 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 precipitating with heptanes