Sodium Hydroxide → 4-Fluorocinnamonitrile

A suspension of 3-(4-fluorophenyl)acrylic acid (2.5 g, 15 mmol) in dry dichloromethane (50 ml) was treated with DMF (2 drops), oxalyl chloride (2.6 ml, 30 mmol) and the reaction was stirred at room temperature under argon for 3 h. The reaction mixture was evaporated to dryness and azeotroped with dichloromethane (25 ml×2) and evaporated to dryness giving a yellow oil. The acid chloride was mixed with sulfolane (15 ml) and treated with sulfamide (1.73 g, 0.018 moles) (A. Hulkenberg and J. J. Troost, Tetrahedron Letters Vol.23, No. 14, 1505-1508, 1982) and the reaction mixture was heated to 120° C. for 3 h. The reaction mixture was cooled, poured into 1N NaOH (100 ml) and extracted with 1:1 diethyl ether:hexane (3×75 ml). The organic extracts were combined, washed with water (3×50 ml), dried (MgSO4) and evaporated to dryness. Purification by flash column chromatography eluted with 2:1 hexane:ethyl acetate gave E-3-(4-fluorophenyl)acrylonitrile as a cream solid (2.12 g, 96%); 1H-NMR (CDCl3) 5.77, 5.83 (1H, d), 7.16 (2H, m), 7.26, 7.40 (1H, d), 7.45 (2H, m). MS (APCI+) M+1=148, C9H6FN requires 147.

1. customThe reaction mixture was evaporated to dryness
2. customazeotroped with dichloromethane (25 ml×2)
3. customevaporated to dryness
4. customgiving a yellow oil
5. temperature14, 1505-1508, 1982) and the reaction mixture was heated to 120° C. for 3 h
6. temperatureThe reaction mixture was cooled
7. extractionextracted with 1:1 diethyl ether
8. washwashed with water (3×50 ml)
9. dry with materialdried (MgSO4)
10. customevaporated to dryness
11. customPurification by flash column chromatography
12. washeluted with 2:1 hexane

ORD record

ord-807ab9910e3d45f89cb8abeeb9aae963

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07462620B2