Water → (4-Fluoro-2-iodophenyl)methanamine

Temperature

55 °C

Triphenylphosphine (13.2 g, 50.4 mmol) was added to 1-(azidomethyl)-4-fluoro-2-iodobenzene (9.31 g, 33.6 mmol) dissolved in dry DMF (20 mL) at 0° C. After one hour water (3.03 mL, 168 mmol) was added and the solution was heated to 55° C. for one hour. The reaction was cooled and the solution was concentrated to about 10 mL in vacuo. The residue was purified in two runs by preparative HPLC (Gilson semi preparative HPLC system using a Waters Delta pak column (3(10×40 mm I.D.) cartridges, C18, 15 μM pore size) eluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 45 mL/min) to give the desired product in 75% purity. Using a Waters OASIS MCX Cartridge (6 g, 35 cc syringe), half of the 75% pure product dissolved in methanol was loaded onto the column pre-equilibrated with a 1:1 solution of water and methanol. The column was washed once with the 1:1 solution and then washed several times with methanol to remove all UV active material. The amine was eluted by washing the column with methanol saturated with ammonia gas. This procedure was repeated on the remaining 75% pure product. The two batches were combined and concentrated in vacuo to give the free base of the desired product as a yellow oil.

1. temperatureThe reaction was cooled
2. concentrationthe solution was concentrated to about 10 mL in vacuo
3. customThe residue was purified in two runs by preparative HPLC (Gilson semi preparative HPLC system
4. washeluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 45 mL/min)

ORD record

ord-e6206cf5d3f04e088557ca520c502f2a

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07323460B2