Triphenylphosphine → 2-Fluoro-4-(3-thienylmethoxy)benzonitrile

Temperature

0 °C

A solution of triphenylphosphine (20 g) in tetrahydrofuran (300 mL) cooled at 0° C. is treated dropwise during 5 minutes with diisopropyl azodicarboxylate (15 mL) and stirred for 15 minutes at 0° C. It is then treated, dropwise, with a solution of 2-fluoro-4-hydroxybenzonitrile (7 g) and 3-thienylmethanol (7 g) in tetrahydrofuran (200 mL) during 2 hours, and stirring is continued at ambient temperature for 18 hours. The mixture is concentrated in vacuo and the residue is dissolved in ethyl acetate (500 mL). This solution is washed with water (200 mL) and aqueous sodium hydroxide solution (1 N), dried over magnesium sulphate and concentrated in vacuo, to give an oil, which is passed through a pad of silica gel (thickness 5 cm) with the aid of dichloromethane. The resulting filtrate is concentrated in vacuo, to give an oil which crystallizes on standing. Recrystallization from isopropyl ether gives 2-fluoro-4-(3-thienyl-methoxy)benzonitrile (6 g), in the form of a white solid, m.p. 63-65° C.

1. additionIt is then treated
2. stirringstirring
3. waitis continued at ambient temperature for 18 hours
4. concentrationThe mixture is concentrated in vacuo
5. dissolutionthe residue is dissolved in ethyl acetate (500 mL)
6. washThis solution is washed with water (200 mL) and aqueous sodium hydroxide solution (1 N)
7. dry with materialdried over magnesium sulphate
8. concentrationconcentrated in vacuo
9. customto give an oil, which
10. concentrationThe resulting filtrate is concentrated in vacuo
11. customto give an oil which
12. customcrystallizes
13. customRecrystallization from isopropyl ether

ORD record

ord-ec860ccaa026449689f84dccbe193050

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211234B1