1-bromo-2-(3-chloropropoxy)benzene synthesis

Yield:-

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 20; for 16 h;

Steps:

Intermediate: 1-Bromo-2-(3-chloropropoxy)benzene

Intermediate: 1-Bromo-2-(3-chloropropoxy)benzene
A solution of 2-bromophenol (0.303 g, 1.751 mmol) in dry N,N-dimethylformamide (15 mL) was treated with potassium carbonate (0.359 g, 2.60 mmol) followed by 1-bromo-3-chloropropane (0.190 mL, 1.912 mmol).
The reaction was stirred at room temperature for 16 hours.
The reaction was diluted with EtOAc (50 mL) and washed with water (2*30 mL) and brine, then dried over sodium sulfate, filtered, and concentrated under reduced pressure.
The residue was purified by Biotage column chromatography (RediSep 12 g SiO₂, 0% (3 CV), 0-60% (30 CV), 25% (2 CV) of ethyl acetate in hexanes).
Product fractions were pooled and concentrated under reduced pressure, affording the product (0.420 g, 1.683 mmol, 96% yield) as a clear oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.55 (dd, J=7.8, 1.5 Hz, 1H), 7.27 (ddd, J=8.4, 7.2, 1.5 Hz, 1H), 6.93 (dd, J=8.3, 1.5 Hz, 1H), 6.85 (td, J=7.6, 1.4 Hz, 1H), 4.19 (t, J=5.8 Hz, 2H), 3.84 (t, J=6.3 Hz, 2H), 2.33-2.26 (m, 2H).
(The material contained bromopropoxy by-product, and was used without further purification in the following step.)

References:

US2017/107202,2017,A1 Location in patent:Paragraph 0642; 0643