A. Phenylmagnesium bromide (Note 1). Ether (100 mL) is added to magnesium (Mg) turnings (74.6 g, 3.07 mol) in a dry, 5-L flask equipped with an overhead stirrer, reflux condenser, and addition funnel. Iodine (several crystals) is added and the mixture is stirred for several minutes (the color dissipates). Bromobenzene (9.23 mL, 13.76 g, 87.64 mmol) is added and the mixture is heated with a heat gun to initiate the reaction. A solution of bromobenzene (322.8 mL, 481 g, 3.06 mol) in ether (600 mL) is added dropwise over 2.75 hr, maintaining a gentle reflux. The dark brown mixture is stirred an additional 3 hr at ambient temperature under nitrogen and then cooled in an ice/methanol bath to 0°C.

B. (R)-(+)-1,1,2-Triphenylethanediol. A solution of methyl (R)-(−)-mandelate (92.3 g, 0.556 mol) (Note 2) in ether (500 mL) (Note 3) is added dropwise to the cold solution of phenylmagnesium bromide prepared in Step A at a rate such that the temperature does not rise above 10°C (1.25 hr required). The mixture is then allowed to stir an additional 2 hr with cooling (final temp 6°C) before heating to reflux. After 3 hr at reflux the solution is allowed to stand overnight at ambient temperature under nitrogen. The solution (CAUTION: Contains benzene) is poured onto 1 kg of ice contained in a 5-L, round-bottomed flask placed in an ice bath and equipped with an overhead stirrer and reflux condenser. A solid mass results that is broken up with a spatula so that it is partly stirrable. Hydrochloric acid (6 N, 516 mL) is added dropwise, while monitoring the pH, to a pH of 3.9. The two-phase, liquid mixture is stirred for 1 hr at ambient temperature. The layers are separated and the aqueous layer is extracted with methylene chloride (CH₂Cl₂) (3 × 250 mL). The combined organic layers are dried (MgSO₄), filtered, and concentrated to a thick caramel-like oil (179 g). Methanol (300 mL) is added causing crystallization and the mixture is heated to reflux to give a clear yellow solution. The solution is allowed to cool to room temperature over several hours. It is then cooled in an ice bath to 0°C and aged for 1 hr. The product is collected on a filter and washed with cold (−10°C) methanol (200 mL). The solid is dried under reduced pressure at 50°C (106.6 g, 66%), mp 123–127°C, [α]²⁰D +220° (95% ethanol, c 1). Liquid chromatographic (LC) analysis shows 96.6% purity with 3.2% benzoin contamination (area %, uncorrected for relative response).

C. (R)-(+)-2-Hydroxy-1,2,2-triphenylethyl acetate [(R)-HYTRA]. Acetyl chloride (32.6 mL, 0.458 mol) in CH₂Cl₂ (85 mL) is added dropwise to R-(+)-triphenylethanediol (103.04 g, 0.355 mol) and pyridine (46.4 mL, 0.574 mol) in CH₂Cl₂ (860 mL) at 0°C (ice/methanol bath). The rate is controlled so that the temperature does not exceed 5°C. After the addition is complete, the mixture is allowed to warm to ambient temperature and aged for 4 hr. LC assay shows 1% unreacted diol. Water (430 mL) is added and the mixture is stirred vigorously for 30 min (pH was 3.5). The mixture is concentrated on a rotary evaporator until second phase CH₂Cl₂ is no longer observed in the distillate or in the reaction mixture. Water (100 mL) is used to aid transfer of the solids to a filter, the filter cake is washed with water (600 mL), and air dried (with suction) overnight. The resulting wet cake is transferred to a 3-L flask equipped with an overhead stirrer, a distillation head, and an addition funnel. Toluene (2 L) is added and the azeotrope is removed by atmospheric distillation. After 480 mL of distillate is collected (80 mL of second phase water), 300 mL of toluene is added; an additional 460 mL of distillate is collected and fresh toluene (500 mL) is added. After 100 mL of clear distillate is collected, fresh toluene (200 mL) is added a third time and the mixture is finally distilled to a 1.5-L mark on the flask (a total of 1620 mL of distillate, including 90 mL of second phase water, is collected). The mixture is allowed to cool overnight with stirring and then cooled to 0°C and aged for 2 hr. The product is collected on a filter, washed with toluene (room temperature, 400 mL) and dried under reduced pressure at 60°C for 7 hr (Note 4); 108.91 g (92.3%), mp 249–251°C, [α]²⁵D +213° (pyridine, c 1), [α]²⁰D +218° (pyridine, c 1). LC analysis shows 100.0% pure (Note 5) and (Note 6).