Diisopropylethylamine → 2,4-dibromo-N-(3-fluoro-4-methylbenzyl)butanamide

To a stirring 0° C. solution of 3-fluoro-4-methylbenzyl amine (2.0 g, 14 mmol) and N-ethyl-N-isopropylpropan-2-amine (3.5 mL, 20 mmol) in dichloromethane (30 mL) was added dropwise a solution of 2,4-dibromobutanoyl chloride (3.98 g, 15 mmol) in dichloromethane (5 mL). After completion of the addition, the reaction was stirred in the ice bath until all of the ice had melted, then it was partitioned between ethyl acetate and water. The layers were separated, the organic layer was washed with brine, and it was then dried over magnesium sulfate. The drying agent was filtered off, the solvent was evaporated, and the residue was dissolved in ethyl acetate and subjected to silica gel chromatography in 10→25→100% ethyl acetate/hexane, collecting the main component to yield 4.5 g (85%) 2,4-dibromo-N-(3-fluoro-4-methylbenzyl)butanamide. LCMS (method CZ-1): RT 1.21 min, m/z 367.9 (MH+); 1H NMR (500 MHz, chloroform-d) δ 7.17 (t, J=7.7 Hz, 1H), 7.01-6.91 (m, 2H), 6.70 (br. s., 1H), 4.59 (dd, J=9.0, 4.9 Hz, 1H), 4.51-4.37 (m, 2H), 3.64-3.51 (m, 2H), 2.71 (dddd, J=15.0, 8.5, 6.1, 4.9 Hz, 1H), 2.51 (ddt, J=15.0, 9.2, 5.5 Hz, 1H), 2.27 (d, J=1.4 Hz, 3H).

1. additionAfter completion of the addition
2. customit was partitioned between ethyl acetate and water
3. customThe layers were separated
4. washthe organic layer was washed with brine, and it
5. dry with materialwas then dried over magnesium sulfate
6. filtrationThe drying agent was filtered off
7. customthe solvent was evaporated
8. dissolutionthe residue was dissolved in ethyl acetate
9. customcollecting the main component

ORD record

ord-8269d541b30f42d4b18cdf1f5a77ac6a

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221796B2