Chlorotrimethylsilane → 3-(Cyclopentyloxy)-4-methoxyphenylacetonitrile

Temperature

0 °C

To a solution of 3-cyclopentyloxy-4-methoxybenzaldehyde (20 g, 90.8 mmol) in acetonitrile (100 mL) was added lithium bromide (15 g, 173 mmol) followed by the dropwise addition of trimethylsilylchloride (17.4 mL, 137 mmol). After 15 min, the reaction mixture was cooled to 0° C., 1,1,3,3-tetramethyldisiloxane (26.7 mL, 151 mmol) was added dropwise and the resulting mixture was allowed to warm to room temperature. After stirring for 3h, the mixture was separated into two layers. The lower layer was removed, diluted with methylene chloride and filtered through Celite. The filtrate was concentrated under reduced pressure, dissolved in methylene chloride and refiltered. The solvent was removed in vacuo to provide a light tan oil. To a solution of this crude a-bromo-3-cyclopentyloxy-4-methoxytoluene in dimethylflormamide (160 mL) under an argon atmosphere was added sodium cyanide (10.1 g, 206 mmol) and the resulting mixture was stirred at room temperature for 18 h, then poured into cold water (600 mL) and extracted three times with ether. The organic extract was washed three times with water, once with brine and was dried (potassium carbonate). The solvent was removed in vacuo and the residue was purified by flash chromatography, eluting with 10% ethyl acetate/hexanes, to provide an off-white solid (17.7 g, 84%): m.p. 32°-34° C.; an additional quantity (1.3 g) of slightly impure material also was isolated.

1. temperatureto warm to room temperature
2. customthe mixture was separated into two layers
3. customThe lower layer was removed
4. additiondiluted with methylene chloride
5. filtrationfiltered through Celite
6. concentrationThe filtrate was concentrated under reduced pressure
7. dissolutiondissolved in methylene chloride
8. customThe solvent was removed in vacuo
9. customto provide a light tan oil
10. extractionextracted three times with ether
11. extractionThe organic extract
12. washwas washed three times with water
13. dry with materialonce with brine and was dried (potassium carbonate)
14. customThe solvent was removed in vacuo
15. customthe residue was purified by flash chromatography
16. washeluting with 10% ethyl acetate/hexanes

ORD record

ord-2ec577b826b343458e113e834842e94a

Source dataset

uspto-grants-1995_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05449686