Toluene → (R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide

Participants

Reaction Conditions

Reaction Steps

Using a jacketed reactor with mechanical stirring at 400 rpm, charge (S)-Hydrobenzoin (292 mg) and toluene (50 mL), followed by Ti(i-PrO)4 (0.20 mL) and water (0.25 mL). Stir the mixture at 20° C. for 30 min. then charge 4-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine (3a, 5.00 g) and stir the mixture for 15 min at 20° C. before being cooling to 0° C. (it took 20 min). Charge TBHP (70% aqueous) (0.75 mL) to the reaction mixture and stir for 23 h at 0° C. Reaction reached 96% conversion and 89% ee. Quench with 5% Na2SO3 (20 mL). Separate the layers and extract the aqueous layer with dichloromethane (50 mL). Combine organic layers and wash with water (20 mL), dry (MgSO4), filter, and concentrate affording the desired sulfoxide in (4.6 g, 88% yield, 89% ee). The product may be recrystallized from THF/water (5:1) with good recovery to yield material >96% ee. NMR (400 MHz, CDCl3) δ 7.16-7.26 (m, 2H), 6.80-6.90 (m, 2H), 3.90-4.20 (m, 4H), 3.75-3.90 (m, 1H), 3.00-3.30 (m, 7H); 13C NMR (400 MHz, CDCl3) δ 177.5, 162.5, 160.7, 149.8, 129.4, 125.7, 123.9, 118.2, 49.6, 46.5, 44.7, 44.4, 33.7 (3 signals missing due to overlap); LCMS (ESI) for C16H17Cl2N4OS (M+H)+: calcd. 383.1, obsvd. 383.0.

Provenance & Evidence