1-(bromomethyl)-2-isopropylbenzene synthesis

Yield:-

Reaction Conditions:

with hydrogen bromide in dichloromethane;water at 20; for 2 h;

Steps:

The organozinc reagent is not commercially available and is prepared from 1- Bromomethyl-2-isopropyl-benzene. This intermediate is synthesised as follows: Add 1.7M te7t-BuLi (26 ml, 44 mmol) dropwise, at-78° C under inert atmosphere, to a solution of 1-Iodo-2-iso-propylbenzene (5g, 20.3 mmol) in 70 ml of dry THE and stir. After 10 min, add Paraformaldehyde (2g, 66.7 mmol) in a single portion. Stir the reaction at this temperature for 15 min and then at room temperature for 2h. Add a saturated aqueous solution of NH4Cl and extract with CH2Cl2 three times. Dry the combined organic extracts over Na2SO4, filter and concentrate under reduced pressure to give a residue. Purify the residue by column chromatography on silica gel eluting with CH2Cl2 to afford pure (2-Isopropyl-phenyl) -methanol as pale purple oil. Add aqueous concentrated HBr (15 ml) to a solution of (2-Isopropyl-phenyl)-methanol (1, 93g, 12.85 mmol) in CH2C12 (15 ml) and stir at room temperature. After 2h. separate phases and wash the organic one with H2O ; dry over Na2SO4 and evaporate at vacuum to obtain a residue. Purify the residue by column chromatography on silica gel eluting with CH2Cl2 to obtain 1-Bromomethyl-2-isopropyl-benzene as very pale pink light oil.'H-NMR (CDC13, 200 MHz) : No. 7.33-7. 25 (m, 3H), 7.19-7. 11 (m, 1H), 4.58 (s, 1H), 3.31 (sep, J= 6.8 Hz, 1H), 1.30 (d, J= 6. 8 Hz, 6H).

References:

WO2005/66144,2005,A1 Location in patent:Page/Page column 40-41