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 3 h, 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 dimethylformamide (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 (K2CO3). The solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel, 10% ethyl acetate/hexanes) to provide an off-white solid (m.p. 32-34° C.); an additional quantity 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. stirringthe resulting mixture was stirred at room temperature for 18 h
11. extractionextracted three times with ether
12. extractionThe organic extract
13. washwas washed three times with water
14. dry with materialonce with brine and was dried (K2CO3)
15. customThe solvent was removed in vacuo
16. customthe residue was purified by flash chromatography (silica gel, 10% ethyl acetate/hexanes)

ORD record

ord-43c63589871f455ea340addc65bdaa78

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06013827