(R)-beta-aminophenethyl alcohol → (5)-N-((R)-2-hydroxy-1-phenylethyl)-2-methyl-5-phenylpentanamide

To a solution consisting of (±)-2,5-dioxopyrrolidin-1-yl 2-methyl-5-phenyl pentanoate (18mb(i), 85.6 g, 296 mmol) in THF (3000 mL) at 48° C. was added R-(−)-2-phenylglycinol (65.9 g, 480 mmol, Bridge Organics) in portions. The resulting reaction mixture was stirred at 48° C. for 40 hours. A white precipitate formed, which was filtered from the reaction mixture and washed with THF. The filtrate was concentrated under vacuum and the residue, comprising the diastereomeric pair, was chromatographed on silica gel. Elution with ethyl acetate-heptane (50:50 v/v) afforded the pure diastereomer title compound (31.3 g, 34%) as a colorless solid; TLC Rf 0.205 (solvent system: 50:50 v/v ethyl acetate-heptane); HPLC retention time 15.1 minutes, stationary phase: Gemini 5μ C18 250×4.6 mm, ultraviolet detector at 210 nm, mobile phase: 1 mL/min, 60:40:0.1 v/v methanol-water-acetic acid.

1. customThe resulting reaction mixture
2. customA white precipitate formed
3. filtrationwhich was filtered from the reaction mixture
4. washwashed with THF
5. concentrationThe filtrate was concentrated under vacuum
6. customwas chromatographed on silica gel
7. washElution with ethyl acetate-heptane (50:50 v/v)

ORD-Eintrag

ord-845b5e6a71054bcaa8d4933eb583801c

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09440919B2