Methyl (S)-2-(Boc-amino)-5-oxo-7-(trimethylsilyl)-6-heptynoate → (2S,5S) 2-tert-Butoxycarbonylamino-5-hydroxy-7-trimethylsilanyl-hept-6-ynoic acid methyl ester

Participants

Reaction Steps

A 50-L flask was charged with the product from Example 1 (2.4.3 kg, 7.11 mol) and isopropanol (29 L). The solution was sparged with dry argon gas for about 50 minutes and the reaction was run under an argon atmosphere. [(1S,2S)—N-(p-toluenesulfonyl)-1,2-diphenylethanediamine](p-cymene) ruthenium (I) (Kanto Chemical Co. Inc. Catalog #41067-95, CAS#188444-42-0, 21.31 g, 0.036 mol) was added under positive argon. The reaction was followed by HPLC and additional charges of catalyst were made (21.31 g, 0.036 mol at 6 hours and 8.27 g, 0.014 mol at 8 hours) and the mixture was stirred at room temperature overnight. After a total of 22 hours, the reaction was complete. The reaction was concentrated and isopropyl acetate was added and the concentration was continued to completely replace the alcohol solvent. The final solution was distilled to about 9 L. Heptane (20 L) was added and the mixture was stirred at room temperature for 30 minutes and at 0° C. for 1 hour. The solid was collected by filtration and the solid was washed with cold heptane (2×4 L) and dried in a vacuum oven at 35-40° C. The procedure gave 2.27 kg (91.5% yield) of white solid. 1H NMR (400 MHz, CDCl3) δ ppm 0.16 (s, 9H) 1.44 (s, 9H) 1.66-1.86 (m, 3H) 1.93-2.06 (m, 1H) 2.18 (d, J=4.67 Hz, 1H) 3.73 (s, 3H) 4.29-4.43 (m, 2H) 5.11 (d, J=7.41 Hz, 1H) 13C NMR (101 MHz, CDCl3) δ ppm 0.24, 28.56, 28.62, 33.42, 52.46, 53.14, 62.14, 79.97, 89.84, 105.77, 116.39, 154.97, 172.55.

Provenance & Evidence