(3-Bromopropoxy)(tert-butyl)dimethylsilane → HCID 9835846, compound

Temperature

-78 °C

A solution of 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile (13.4 g, 60 mmol) in THF (450 mL) was added to a solution of LDA (76 mmol) in THF (30 mL) at −78° C. under an atmosphere of nitrogen. After stirring at −78° C. for 30 min, a solution of (3-bromopropoxy)-tert-butyldimethylsilane (16.8 mL, 72 mmol) in THF (30 mL) was added and the resulting mixture was allowed to warm to room temperature and stirred for 2 h. Then the mixture was poured into ice/H2O (400 mL), and extracted with Et2O (3×500 mL). The organic extracts were washed with H2O (500 mL) and brine (500 mL), dried and evaporated. The residue was dissolved in methanol (400 mL) and was added 1M HCl (200 mL). The resulting solution was stirred at room temperature for 1 h and evaporated. Silica gel chromatography (heptane, EtOAc 5:1) of the residue gave the title product as an oil (14.4 g, 81%). 1H NMR (DMSO-d6) δ1.25 (2H, m); 2.18 (2H, t, J=8.8 Hz); 3.31 (2H, q, J=6.2 Hz); 4.34 (1H, t, J=6.2 Hz); 5.12 (1H, d, J=13.2 Hz); 5.17 (1H, d, J=13.2 Hz); 7.15 (2H, t, J=8.8 Hz); 7.58 (2H, dd, J=6.0 and 8.8 Hz); 7.72 (1H, s); 7.78 (2H, br d, J=6.0 Hz.). 13C NMR (DMSO-d—6) δ27.4; 37.3; 59.8; 71.0; 90.7; 110.5; 114.8; 115.2; 118.8; 123.2; 125.6; 126.9; 127.1; 132.0; 139.9; 140.6; 149.5; 160.9; 162.0.

1. temperatureto warm to room temperature
2. stirringstirred for 2 h
3. extractionextracted with Et2O (3×500 mL)
4. washThe organic extracts were washed with H2O (500 mL) and brine (500 mL)
5. customdried
6. customevaporated
7. dissolutionThe residue was dissolved in methanol (400 mL)
8. additionwas added 1M HCl (200 mL)
9. stirringThe resulting solution was stirred at room temperature for 1 h
10. customevaporated

ORD record

ord-cbf0eca0f77c432184e46586142e2a0d

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06420574B1