Methyl 2-Bromo-5-chlorobenzoate → HCID 46856402, compound

Temperature

-78 °C

A THF solution of sodium bis(trimethylsilyl)amide (1.0M, 194 mL, 194 mmol) was added dropwise to a −78° C. THF (400 mL) solution containing methyl 2-bromo-5-chlorobenzoate (16.10 g, 64.5 mmol) and 4,4,4-trifluorobutyric acid (9.17 g, 64.5 mmol). After stirring for 15 minutes at −78° C. the solution was warmed to 0° C. and stirred for an additional 2 hours. The reaction was quenched with an excess of aqueous 1N HCl (ca 400 mL) and stirred overnight at room temperature. The solution was concentrated to remove the majority of the THF. The solution was then diluted with EtOAc and washed with 1N NaHCO3 (twice) and brine. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated compound (solid). 1H NMR (500 MHz, CDCl3): δ 7.58 (d, J=8.4 Hz, 1H); 7.41 (d, J=2.5 Hz, 1H); 7.33 (dd, J=8.5, 2.5 Hz, 1H); 3.22 (t, J=7.8 Hz, 2H); 2.68-2.56 (m, 2H).

1. temperaturewas warmed to 0° C.
2. stirringstirred for an additional 2 hours
3. customThe reaction was quenched with an excess of aqueous 1N HCl (ca 400 mL)
4. stirringstirred overnight at room temperature
5. concentrationThe solution was concentrated
6. customto remove the majority of the THF
7. additionThe solution was then diluted with EtOAc
8. washwashed with 1N NaHCO3 (twice) and brine
9. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by silica gel chromatography
13. customto give the indicated compound (solid)

ORD record

ord-d5d1dc20aa974f8682ae9d291f9d24af

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365574B2