Potassium Carbonate → 4-(4-Hydroxybut-1-yn-1-yl)benzonitrile

Temperature

80 °C

Potassium carbonate (376.7 g, 2.5 mol eq.) was dissolved in a mixture of 1,2-dimethoxyethane (DME, 1.2 L, 6 vol) and water (1.2 L, 6 vol). Palladium on charcoal (20 g, 0.01 mol eq., 10% Johnson Matthey type 87L, 60% water), triphenylphosphine (11.5 g, 0.04 mol eq.) and copper(I) iodide (4.2 g, 0.02 mol eq.) were added. 4-Bromobenzonitrile (200 g, 1 mol eq.) was then added, washing in with a mixture of DME (200 mL, 1 vol) and water (200 mL, 1 vol). This mixture was stirred rapidly under nitrogen for a minimum of thirty minutes. A solution of but-3-yn-1-ol (92.1 mL, 1.1 mol eq) in DME (200 mL, 1 vol) and water (200 mL, 1 vol) was added dropwise over five minutes. The combined mixture was then heated to 80° C. for three hours. The reaction was monitored by HPLC for the disappearance of arylbromide and the formation of sub-title compound. Once all of the starting material had been consumed, the reaction was cooled to 25° C. and filtered through kieselguhr. The filter cake was washed separately with toluene (1.6 L, 8 vol). The DME:water mixture was partially concentrated in vacuo to remove the majority of the DME. This was then partitioned with the toluene wash. The toluene layer was concentrated in vacuo to give sub-title alkyne as a yellow solid, which was dried in a vacuum oven overnight at 40° C. Yield 182.88 g, 97%.

1. washwashing in with a mixture of DME (200 mL, 1 vol) and water (200 mL, 1 vol)

ORD record

ord-fc46d2d8d8234c039f532d7a6c7afb03

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07217708B2