Nadide → HCID 12163515, compound

Participants

Reaction Conditions

Reaction Steps

To 800 mL of 0.2M, pH 6.0 sodium phosphate buffer in a 2 L flask equipped with an overhead stirrer was added D-glucose (38.6 g, 1.2 eq), β-nicotinamide adenine dinucleotide, free acid (1.6 g, mmol), glucose dehydrogenase (36 mg, 3.2 kU, CODEXIS® GDH-102, 90 U/mg), and enzyme KRED-NADH-110 (200 mg, CODEXIS®, 25 U/mg). The vessels containing the reagents above were rinsed with 200 mL of fresh sodium phosphate buffer and added to the reaction which was stirred to dissolution and then heated to 40° C. To this mixture was added a solution of 2-bromo-4′-cyanoacetophenone (40 g, 178.5 mmol) in 100 mL DMSO through an addition funnel in about 30 min. The container was rinsed with 20 mL DMSO and the rinse was added to the reactor. A pH of 5.5-6.0 was maintained by adding 1 M NaOH through a fresh addition funnel (total volume of 200 mL over 6 h) after which HPLC showed complete consumption of the starting material. The reaction mixture was extracted with 800 mL MTBE×2 and the combined extracts were washed with 300 mL of 25% brine. The crude alcohol was transferred to a 3 L 3-neck flask and treated with solid NaOtBu (34.3 g, 357 mmol) stirring for 1 h and then additional NaOtBu (6.9 g, 357 mmol) and stirring for 30 min. The reaction mixture was filtered and the solution was washed with 300 mL 0.2 M pH 6.0 sodium phosphate buffer, brine, and then the solvent was removed in vacuo and the resulting white solid was dried in a vacuum oven to give (S)-4-(oxiran-2-yl)benzonitrile (23 g, 90% yield, 100% e.e.). 1H NMR (400 MHz, CDCl3) δ ppm 7.62 (2H, d), 7.35 (2H, d), 3.88 (1H, dd), 3.18 (1H, app t), 2.73 (1H, dd) Purity=99%.

Provenance & Evidence