Triphenylphosphine → 2-Fluoro-4-(isothiazol-4-ylmethoxy)benzonitrile

Diisopropyl azodicarboxylate (1.19 g) is added to a stirred solution of triphenylphosphine (1.55 g) in tetrahydrofuran (30 mL) at 0° C. under nitrogen and stirring is continued at 0° C. for 30 minutes. A solution of isothiazol-4-ylmethanol (0.34 g) and 2-fluoro-4-hydroxybenzonitrile (0.4 g) in tetrahydrofuran (30 mL) is added at such a rate that the temperature did not exceed 0° C. After the addition is complete stirring is continued at 0° C. for 30 minutes then at ambient temperature for 24 hours. The reaction mixture is concentrated in vacuo and the residue is partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase is washed with water (50 mL), with brine (50 mL), dried over magnesium sulphate and evaporated. The residue is purified by flash chromatography on silica eluting with dichloromethane. Fractions homogeneous in the required product are combined and evaporated to give 2-fluoro-4-(isothiazol-4-ylmethoxy)benzonitrile (0.24 g), m.p. 102-105° C.

1. customdid not exceed 0° C
2. additionAfter the addition
3. stirringis complete stirring
4. waitis continued at 0° C. for 30 minutes
5. waitat ambient temperature for 24 hours
6. concentrationThe reaction mixture is concentrated in vacuo
7. customthe residue is partitioned between ethyl acetate (50 mL) and water (50 mL)
8. washThe organic phase is washed with water (50 mL), with brine (50 mL)
9. dry with materialdried over magnesium sulphate
10. customevaporated
11. customThe residue is purified by flash chromatography on silica eluting with dichloromethane
12. customevaporated

ORD record

ord-d335481e652f416587082d0f8b066f87

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211234B1