Tetraethyltin → 3-Methoxy-4-ethyl-benzonitrile

Temperature

80 °C

To a solution of 3-methoxy-4-hydroxybenzonitrile (9-1, 2.0 g, 13.4 mmol) in DCM (67 mL) at −78 deg was added DIPEA (3.0 mL, 17.4 mmol) followed by Triflic Anhydride (2.7 mL, 16.0 mmol) and stirred at −78 deg 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 (0.491 g, 0.960 mmol) and LiCl (1.22 g, 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 (9-2) 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. customThe mixture was partitioned between saturated NaHCO3 and EtOAc
10. washThe organic phase was washed with water, brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude material was purified by gradient elution on silica gel (0 to 20% EtOAc in hexanes)

ORD record

ord-e776887cc3cb49bb814c8e22dd23c4d5

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399494B2