Allyl bromide → Methyl 2-(3,4-dichlorophenyl)pent-4-enoate

Temperature

-78 °C

To a solution of N,N-diisopropylamine (1.79 mL, 12.8 mmol) in tetrahydrofuran (10.0 mL, 123 mmol) was added 2.50 M of n-butyllithium in hexane (4.68 mL, 11.7 mmol) dropwise at 0° C. The solution was stirred under an atmosphere of Nitrogen for 10 min, and then cooled to −78° C. A solution of methyl 3,4-dichlorophenylacetate (2.27 g, 10.4 mmol) in tetrahydrofuran (10.0 mL) was added to the LDA solution dropwise via cannula. After 10 min of stirring, the reaction was warmed to 0° C. for 1 hr. The solution was cooled back to −78° C., and allyl bromide (2.24 mL, 25.9 mmol) was added in one portion. In 10 min, the reaction was warmed back to 0° C. After 1 hr of stirring, the reaction was quenched with NH4Cl sat soln and extracted with EtOAc (×3). The combined organic layer was dried and concentrated to provide an orange oil. Further purification on a silica gel column (gradient elution, 0-10% EtOAc/hexanes) provided methyl 2-(3,4-dichlorophenyl)pent-4-enoate as a colorless oil (2.47 g, 92.0% yield). 1H NMR (400 MHz, CDCl3) δ 7.43-7.37 (m, 2H), 7.18-7.12 (dd, J=8.3, 2.1 Hz, 1H), 5.73-5.60 (ddt, J=17.1, 10.2, 6.8 Hz, 1H), 5.12-4.98 (m, 2H), 3.70-3.64 (s, 3H), 3.63-3.55 (t, J=7.8 Hz, 1H), 2.85-2.71 (m, 1H), 2.55-2.43 (m, 1H).

1. stirringAfter 10 min of stirring
2. temperaturethe reaction was warmed to 0° C. for 1 hr
3. temperatureThe solution was cooled back to −78° C.
4. waitIn 10 min
5. temperaturethe reaction was warmed back to 0° C
6. stirringAfter 1 hr of stirring
7. customthe reaction was quenched with NH4Cl
8. extractionextracted with EtOAc (×3)
9. customThe combined organic layer was dried
10. concentrationconcentrated
11. customto provide an orange oil
12. customFurther purification
13. washon a silica gel column (gradient elution, 0-10% EtOAc/hexanes)

ORD record

ord-abac34e015d84f4eb3faffadfdadc790

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796271B2