(1S,2S,4R)-2-(hydroxymethyl)-4-(tritylamino)cyclopentan-1-ol → (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol

Participants

Reaction Conditions

Reaction Steps

A hydrogenation reactor was purged with argon and charged with 5% palladium on carbon (50% water wet, 80 g, 20 mol %) and the reactor sealed. Using vacuum, a solution of (1S,2S,4R)-2-(hydroxymethyl)-4-(tritylamino)cyclopentanol (400 g, 1.07 mol) in methanol (2.7 L) was added to the reactor. The reactor was purged with argon, charged to 35 to 45 psi hydrogen and heated to 35° C. for 72 h. The reaction mixture was filtered through a pad of diatomaceous earth, washed with methanol (32 L) and concentrated under reduced pressure to ˜1 L volume. Precipitated triphenyl methane was filtered from the mixture and the filtrate further concentrated to give an amber oil. The crude material was purified by silica-gel chromatography. The column was performed as follows. A 15 cm diameter glass column was loaded with a slurry of silica gel (1.6 kg) in methylene chloride. The amber oil was adsorbed onto silica gel (200 g) and loaded on the column. The polarity was gradually increased from 100% methylene chloride to 50% methylene chloride/methanol. The pure fractions were combined and concentrated under reduced pressure to afford the title compound (118 g) as a waxy yellow solid. 1H NMR (300 MHz, CD3OD, δ): 4.35-4.32 (m, 1H), 3.76-3.70 (m, 1H), 3.64-3.56 (m, 2H), 2.34-2.26 (m, 1H), 2.10-2.03 (m, 1H), 1.93-1.82 (m, 1H) and 1.63-1.46 (m, 2H).

Provenance & Evidence