Hydrogen Bromide → 1-(Bromomethyl)-4-chloro-2,5-dimethoxybenzene

(Bloomer et al., Tetrahedron Lett. 1989, 30, 1201-1204.) To a stirred solution of 2 (5.00 g, 24.7 mmol, 1 equiv) in CH2Cl2 (125 mL) at 0° C. was added dropwise HBr (47-49% solution; 4.13 mL, 74.0 mmol, 3 equiv). The resulting solution was allowed to slowly warm to room temperature and stir overnight (˜16 h). The following morning a second batch of HBr (47-49% solution; 4.13 mL, 74.0 mmol, 3 equiv) was added to the reaction mixture, which was allowed to stir for an additional 4 h. The crude mixture was extracted with Et2O (×2), washed with water, a saturated aqueous solution of NaHCO3, brine, dried (MgSO4), filtered, and concentrated under reduced pressure to give 6.55 g (100% yield) of 3 as a white solid: Mp 85-88° C.; Rf 0.31 (EtOAc/hexanes, 3:7); IR (neat) 2962, 2947, 2844, 1732, 1582, 1495, 1458, 1443, 1389, 1301, 1204, 1182, 1033, 882 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.91-6.90 (m, 2 H), 4.50 (s, 2 H), 3.84 (s, 3 H), 3.82 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 151.3, 148.9, 125.1, 123.2, 114.6, 113.6, 56.6, 56.2, 28.2.

1. stirringto stir for an additional 4 h
2. extractionThe crude mixture was extracted with Et2O (×2)
3. washwashed with water
4. dry with materiala saturated aqueous solution of NaHCO3, brine, dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure

ORD record

ord-e24b483612d14e22ad27547e56cae5a5

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169182B2