Phosphonium, (2-methoxy-2-oxoethyl)triphenyl-, bromide (1:1) → methyl (E)-3-[3-bromo-5-(1-cyanocyclopropyl)phenyl]prop-2-enoate

Temperatur

-25 °C

To a suspension of (2-methoxy-2-oxo-ethyl)-triphenyl-phosphonium bromide (1.502 g, 3.618 mmol) in THF (15 mL) under nitrogen at room temperature was added LHMDS in THF (3.358 mL of 1 M, 3.358 mmol) dropwise. The mixture was stirred for 10 mins then cooled to −25° C. 1-(3-bromo-5-formyl-phenyl)cyclopropane-1-carbonitrile (500 mg, 1.999 mmol) was dissolved in 1 mL of THF and added to the reaction. The reaction was allowed to warm to room temperature over 1 hour. The reaction was quenched with MeOH (2 mL) and then partitioned between ethyl acetate and brine. The aqueous was extracted with ethyl acetate and dried, filtered and concentrated. The crude product was purified on silica (Companion, 24 g) eluting with 1-20% EtOAc:Petrol ether to give methyl (E)-3-[3-bromo-5-(1-cyanocyclopropyl)phenyl]prop-2-enoate as a yellow solid (594 mg, 97%).

1. additionadded to the reaction
2. temperatureto warm to room temperature over 1 hour
3. customThe reaction was quenched with MeOH (2 mL)
4. custompartitioned between ethyl acetate and brine
5. extractionThe aqueous was extracted with ethyl acetate
6. customdried
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified on silica (Companion, 24 g)
10. washeluting with 1-20% EtOAc

ORD-Eintrag

ord-65b330ad44924c08be48c7f91ca5f2d5

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08173635B2