The 3,4,5-trifluorobenzyl bromide can be obtained from 3,4,5-trifluorobenzaldehyde by first preparing (3,4,5-trifluorophenyl)methanol as raw material and then brominating to obtain 3,4,5-trifluorobenzyl bromide.
Step A: (3,4,5-Trifluorophenyl)methanol:
To a cooled (-5C) solution of 3,4,5-trifluorobenzaldehyde (7.0 g, 43.75 mmol) in a mixture of THF and water (50 ml, 9:1) was added slowly in batches over a period of 30 min, NaBH4 (1.662 g, 43.75 mmol). This reaction mixture was brought to room temperature over a period of 2h and carefully poured into ice-cold dilute HCl (200 ml, 1N). The oil layer was extracted into CH2Cl2 (250 ml) and the organic layer was washed with water (200 ml), dried (MgSO4) and evaporated. The resulting crude product (7.08 g, quantitatively) was continued without further purification.
Step B: 3,4,5-Trifluorobenzyl bromide:
To a solution of (3,4,5-trifluorophenyl)methanol (40 mmol) in CH2Cl2 (150 ml) was slowly added a solution of thionyl bromide (6.16 ml, 80 mmol) in CH2Cl2 (50 ml). This reaction mixture was stirred for 16h at room temperature and poured into ice water (200ml). The organic layer was separated, washed with saturated NaHCO3 (2 x 200 ml), water (200 ml), dried (MgSO4) and evaporated to give the corresponding light yellow oily bromo compound in quantitative yield.
