2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene

172900-70-8

172900-69-5

Example 1 Synthesis of (R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl bromide: (R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol (14.82 g, 50 mmol) was dissolved in N,N-dimethylformamide (234 mL), and phosphorus tribromide ( 14.33 g, 50 mmol) and the reaction temperature was controlled at 20 °C. The reaction mixture was stirred at 20 °C for 8 hours. After the reaction was completed, it was cooled to room temperature and the reaction solution was slowly poured into water (702 mL) and extracted three times with hexane. The hexane layers were combined and washed twice each with saturated sodium bicarbonate solution and saturated sodium chloride solution in turn. The organic layer was dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated to give 17 g of oily product. Methanol (51 mL) was added to the oily product and the product was crystallized at a controlled temperature of -10°C. The crystals were collected by filtration. The crystals were collected by filtration and dried under vacuum at room temperature to give 14.3 g of white solid in 79.6% yield, melting point 51-53 °C, chiral purity ≥99.9%.1H NMR (ppm, CDCl3): δ 6.72-6.81 (m, 3H), 4.11 (t, J = 6.4 Hz, 2H), 3.84 (s, 3H), 3.58 (t, J = 6.4 Hz, 2H), 3.42 (dd, J = 4.5, 10.2 Hz, 1H), 3.36 (s, 3H), 3.30 (dd, J = 4.5, 10.2 Hz, 1H), 2.77 (dd, J = 4.8, 13.8 Hz, 1H), 2.48 (dd, J = 4.8, 13.8 Hz, 1H), 2.11 (m, 2H ), 1.86 (m, 1H), 1.60 (m, 1H), 0.99 (m, 6H).