Trifluoroacetic acid → (3r,4r,5r)-3-Amino-4,5-dimethyloctanoic acid

To the solution of (4R,5R)-4,5-dimethyl-(R)-3-(toluene-4-sulfinylamino)-octanoic acid tert-butyl ester (1.8 g, 4.71 mmol) in dry methanol (30 mL) at 0° C. under nitrogen was added excess trifluoroacetic acid (25 mL) and stirred for 2 hours at that temperature. The solution was concentrated to dryness followed by the addition of dry dichloromethane (20 mL) and trifluoroacetic acid (20 mL). The resulting mixture was stirred for 2 hours under nitrogen and concentrated to dryness. The residue was applied to BondElute SCX ion exchange resin and eluted with water until the eluent was at constant pH of 6.5. The resin was then eluted with a 1:1 solution of methanol and with 10% ammonium hydroxide solution. The ammonium hydroxide solution was evaporated and the residue was crystallized with methanol-acetonitrile mixture to afford the titled compound (0.717 g, 81.2% yield) as a white solid: 1H NMR (400 MHz, CD3OD-D) δ ppm 0.9 (m, 11H) 1.1 (m, 2H) 1.3 (m, 1H) 1.4 (m, 1H) 1.6 (m, 1H) 1.7 (m, 2H) 2.3 (dd, J=16.6, 10.0 Hz, 1H) 2.5 (dd, J=16.7, 3.5 Hz, 1H) 3.3 (m, 1H). MS, m/z (relative intensity): 188 [M+1H, 100%], 186 [M−1H, 100%].

1. concentrationThe solution was concentrated to dryness
2. additionfollowed by the addition of dry dichloromethane (20 mL) and trifluoroacetic acid (20 mL)
3. stirringThe resulting mixture was stirred for 2 hours under nitrogen
4. concentrationconcentrated to dryness
5. washeluted with water until the eluent
6. washThe resin was then eluted with a 1:1 solution of methanol and with 10% ammonium hydroxide solution
7. customThe ammonium hydroxide solution was evaporated
8. customthe residue was crystallized with methanol-acetonitrile mixture

ORD-Eintrag

ord-b642dc13fc6c4ff0b7dbc16e041333cc

Quelldatensatz

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07388023B2