4-Methylmorpholine → HCID 59444289, Verbindung

A dry 250 ml 3-neck flask, equipped with a reflux condenser and a thermometer, was charged with (R)-3-(methoxycarbonyl)-4-methylpentanoic acid (1.6 g, 9.19 mmol, which was prepared according to the procedure described in Robert J. Cregge et al., J. Med. Chem. 1998, 41, 2461-2480) and anhydrous acetonitrile (60 mL) under Argon. To the mixture was added N-methylmorpholine (2.020 mL, 18.37 mmol) followed by diphenylphosphoryl azide (1.979 mL, 9.19 mmol), and the mixture was stirred at rt for 1.5 hrs. After this time, 2-(trimethylsilyl)ethanol (6.58 mL, 45.9 mmol) was added to the mixture and the mixture was heated at 85° C. with stirring for 1 hr and 40 minutes. After cooling to rt, the solvent was evaporated off and the resulting residue was dissolved in EtOAc (˜100 ml). The resulting solution was washed with water, sat'd NaHCO3 (2×), 1N HCl and brine; dried over Na2SO4 and evaporated to give an oily residue. The oily residue was purified by Combiflash chromatography (220 g silica gel) eluting with 2:8 EtOAc-hexane to give 1.22 g of title compound. 1H NMR (CDCl3, 400 MHz) δ ppm 4.95 (1 H, br. s.), 4.03-4.22 (2 H, m), 3.70 (3 H, s), 3.40-3.54 (1 H, m), 3.23-3.34 (1 H, m), 2.38-2.53 (1 H, m), 1.97 (1 H, dq, J=13.62, 6.81 Hz), 1.26 (6 H, t, J=7.14 Hz), 0.97 (3 H, d, J=7.03 Hz), 0.94 (3 H, d, J=6.81 Hz), 0.00 (9 H, s).

1. customA dry 250 ml 3-neck flask, equipped with a reflux condenser
2. customwas prepared
3. temperaturethe mixture was heated at 85° C.
4. stirringwith stirring for 1 hr and 40 minutes
5. temperatureAfter cooling to rt
6. customthe solvent was evaporated off
7. dissolutionthe resulting residue was dissolved in EtOAc (˜100 ml)
8. washThe resulting solution was washed with water
9. dry with materialdried over Na2SO4
10. customevaporated
11. customto give an oily residue
12. customThe oily residue was purified by Combiflash chromatography (220 g silica gel)
13. washeluting with 2:8 EtOAc-hexane

ORD-Eintrag

ord-bce9c8cf52bf464c908dd45d7bbea7f5

Quelldatensatz

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08501782B2