Tetrahydrofuran → 1-Bromo-4-(1-bromoethyl)benzene

Temperature

-78 °C

To a 50 mL round-bottomed flask containing polystyrene resin (5 Scheme 18, 200 mg, 0.30 mequiv/g) in dry THF (15 mL) at −78° C. was added methylmagnesium bromide (10 equiv). The reaction slurry was stirred for 1 h at −78° C., then warmed slowly to room temperature and further stirred for 2 h. After cooling the flask to −20° C., saturated NH4Cl (0.5 mL) was added, and the mixture was stirred for 20 min at room temperature. The resin was filtered and washed with 1:1 THF/water (twice), water (twice), methanol (twice), CH2Cl2 (twice), then dried under reduced pressure. To a slurry of resin in CH2Cl2 (8 mL) was added Br2 (100 μL). After agitation for 20 min, the cleavage solution was removed, and the resin was rinsed with CH2Cl2 (5 mL). Concentration of the combined filtrates gave 4-bromo-α-methyl benzyl bromide (7 Scheme 18) as a colorless oil (12 mg, 75%); 1H NMR (300 MHz, CDCl3) δ 2.03 (d, J=6.97 Hz, 3 H), 5.17 (q, J=6.97 Hz, 1 H), 7.32 (d, J=8.49, 2 H), 7.49 (d, J=8.49, 2 H); 13C NMR (75 MHz, CDCl3) 27.0, 48.5, 122.4, 128.8 (2C), 132.1 (2C), 142.5.

1. temperaturewarmed slowly to room temperature
2. stirringfurther stirred for 2 h
3. temperatureAfter cooling the flask to −20° C.
4. stirringthe mixture was stirred for 20 min at room temperature
5. filtrationThe resin was filtered
6. washwashed with 1:1 THF/water (twice), water (twice), methanol (twice), CH2Cl2 (twice),
7. customthen dried under reduced pressure
8. additionTo a slurry of resin in CH2Cl2 (8 mL) was added Br2 (100 μL)
9. waitAfter agitation for 20 min
10. customthe cleavage solution was removed
11. washthe resin was rinsed with CH2Cl2 (5 mL)

ORD record

ord-0259ebb8e9cc434fa34eea3dd1601c6e

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06416861B1