Tetraethyltin → 3-Methoxy-4-ethyl-benzonitrile

Temperature

-78 °C

To a solution of 3-methoxy-4-hydroxybenzonitrile (13-1, 2.0 g, 13.4 mmol) in DCM (67 mL) at −78° C. was added diisopropylethylamine (3.0 mL, 17.4 mmol) followed by triflic anhydride (2.7 mL, 16.0 mmol) and stirred at −78° C. for 1 h. The mixture was poured into a separatory funnel containing a few pieces of ice and then partitioned between ice water and ether. The organic phase was washed with 1N HCl and then 10% Na2CO3, dried over Na2SO4, filtered and concentrated to yield a pale yellow oil. To a solution of this oil (2.7 g, 9.60 mmol) in DMF (96.0 mL) was added tetraethyl tin (3.80 mL, 19.2 mmol), bis(tri-t-butylphosphine) palladium(0) (0.491 g, 0.960 mmol) and LiCl (1.22g, 28.8 mmol) and the system was heated to 80° C. for 1 h in an oil bath. The mixture was partitioned between saturated NaHCO3 and EtOAc. The organic phase was washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by gradient elution on silica gel (0 to 20% EtOAc in hexanes) to afford the desired compound (13-2) as a pale yellow crystalline solid. ESI+MS [M+H]+ C10H11NO: 162.1 found, 162.2 required.

1. additionThe mixture was poured into a separatory funnel
2. additioncontaining a few pieces of ice
3. custompartitioned between ice water and ether
4. washThe organic phase was washed with 1N HCl
5. dry with material10% Na2CO3, dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield a pale yellow oil
9. temperaturethe system was heated to 80° C. for 1 h in an oil bath
10. customThe mixture was partitioned between saturated NaHCO3 and EtOAc
11. washThe organic phase was washed with water, brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customThe crude material was purified by gradient elution on silica gel (0 to 20% EtOAc in hexanes)

ORD record

ord-0315c62550ec4c0d9752eec079023425

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003797B2