Sodium Hydroxide → (E)-Methyl 3-chloro-2-(2-cyanovinyl)benzoate

To 4-chloroisobenzofuran-1,3-dione (1.82 g, 10 mmol) in tetrahydrofuran (20 mL) was added lithium tri-tert-butoxyaluminum hydride (0.5 M, 20 mL, 10 mmol, diglyme) at −20° C. The mixture was stirred at room temperature overnight. (Triphenylphosphoranylidene)acetonitrile (3.0 g, 10 mmol) was added, and the resultant mixture was heated at 120° C. for 16 hours. 2 N Sodium hydroxide(aq) was added and the mixture was extracted with ethyl acetate (2×). HCl(aq) (1 M) was added to the aqueous layer to pH3, and the mixture was extracted with ethyl acetate. The organic extracts was dried and concentrated. The residue was dissolved in 20 mL of 1:1 CH2Cl2:methanol followed by the addition of (trimethylsilyl)diazomethane (4 mL, 2 N in diethyl ether, 8 mmol). The mixture was stirred for 1 hour and quenched with acetic acid. The mixture was concentrated and purified by silica gel column chromatography eluting with 2:1 hexanes:ethyl acetate to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.85 (dd, J=1.0, 7.5 Hz, 1H), 7.81 (dd, J=1.0, 8.0 Hz, 1H), 6.04 (d, J=17 Hz, 1H), and 3.84 (s, 3H).

1. extractionthe mixture was extracted with ethyl acetate (2×)
2. additionHCl(aq) (1 M) was added to the aqueous layer to pH3
3. extractionthe mixture was extracted with ethyl acetate
4. customThe organic extracts was dried
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in 20 mL of 1:1 CH2Cl2
7. stirringThe mixture was stirred for 1 hour
8. customquenched with acetic acid
9. concentrationThe mixture was concentrated
10. custompurified by silica gel column chromatography
11. washeluting with 2:1 hexanes

ORD record

ord-33e43648740e404e89c6ce21cec9b64f

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846951B2