Hydrochloric Acid → 1616359-84-2

Temperature

-70 °C

To a solution of oxalyl chloride (0.58 mL, 6.9 mmol) in DCM (20 mL) was added dropwise a solution of dimethylsulfoxide (1.11 mL, 15.6 mmol) in DCM (10 mL), at temperature lower than −65° C. The resulting mixture was stirred for about 20 min at about −70° C. Then a solution of (2-bromo-4-chloro-5-methoxy-phenyl)methanol (1.56 g, 6.2 mmol) in DCM (20 mL) was added dropwise at temperatures lower than −65° C., and the resulting mixture was stirred for about another 20 min. Subsequently, TEA (3.52 mL, 25.2 mmol) was added dropwise at temperatures lower than −70° C., and the mixture was stirred for about 10 min at about −70° C. The mixture was allowed to warm to rt and stirred for about 16 h, treated with 1 M aqueous HCl (100 mL) and DCM (50 mL). The layers were separated and the aqueous layer was extracted with DCM (100 mL). The combined organic layers were washed with water (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, diethyl ether/hexanes 5:95) to give 2-bromo-4-chloro-5-methoxybenzaldehyde (1.48 g, 5.9 mmol, 95%) as a white solid: 1H-NMR (CDCl3, Bruker 400 MHz) δ 3.96 (3 H, s), 7.46 (1 H, s), 7.68 (1 H, s), 10.3 (1 H, s).

1. customlower than −65° C
2. stirringthe resulting mixture was stirred for about another 20 min
3. stirringthe mixture was stirred for about 10 min at about −70° C
4. temperatureto warm to rt
5. stirringstirred for about 16 h
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with DCM (100 mL)
8. washThe combined organic layers were washed with water (50 mL)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by column chromatography (SiO2, diethyl ether/hexanes 5:95)

ORD record

ord-5e1f4741736a4166a1b53bb178723c79

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2