(4-bromo-2-methylphenyl)methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Bromo-2-methylphenyl)methanol (10.4 g, 51.6 mmol) is dissolved in anhydrous CH2Cl2 (150 mL) and CBr4 (18.8 g, 56.8 mmol) added. The reaction mixture is cooled to 0-5° C. and PPh3 (14.9 g, 56.8 mmol) is added. The reaction mixture is stirred overnight then hexane/EtOAc (9:1) (250 mL) is added with vigorous stirring. The triphenylphosphine oxide that forms during the reaction is filtered off and the filtrates are concentrated in vacuo. The resulting oil is purified on a silica gel pad with hexane/EtOAc (8:2). The solvent are removed on a rotary evaporator and the bromoform is removed by vacuum distillation (15 mm Hg, bp: 40-50° C.) to provide the expected product 1-Bromo-4-(bromomethyl)-3-methylbenzene (13.23 g, 97%) as a yellow oil. 1H NMR (300 MHz, CHLOROFORM-D): δ 7.37-7.27 (2H, m), 7.17 (1H, d, J=8.1 Hz), 4.45 (2H, s), 2.39 (3H, s). is filtered off the filtrates are concentrated in vacuo The resulting oil is purified on a silica gel pad with hexane/EtOAc (8:2) The solvent are removed on a rotary evaporator the bromoform is removed by vacuum distillation (15 mm Hg, bp: 40-50° C.)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-methylbenzoic acid (11.1 g, 51.6 mmol) is dissolved in anhydrous THF (11.2 mL). The solution is cooled to 0-5° C. and a 1 M solution of BH3. THF (103 mL) is added to the mixture. The solution is left stirring 3 h at room temperature. Cold water is then added (20 mL) and the reaction mixture is washed with a saturated solution of NaHCO3 (120 mL). The aqueous phase is extracted with diethyl ether (3×300 mL) and the combined organic phases washed with brine (200 mL), dried with MgSO4 and concentrated in vacuo. The resulting oil is purified by flash-chromatography, eluting with hexane/EtOAc from 95:5 to 70:30, to provide the expected product (4-Bromo-2-methylphenyl)methanol (10.4 g, 100%) as a clear oil. The solution is left the reaction mixture is washed with a saturated solution of NaHCO3 (120 mL) The aqueous phase is extracted with diethyl ether (3×300 mL) the combined organic phases washed with brine (200 mL) dried with MgSO4 concentrated in vacuo The resulting oil is purified by flash-chromatography eluting with hexane/EtOAc from 95:5 to 70:30