Reaktion #421076

Reaktionsgleichung

(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

3-hydroxy-3-methyl-1-butyne

→

title compound

Ausbeute 89.0%

(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(3-hydroxy-3-methylbut-1-ynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

Ausbeute 89.0%

Lösungsmittel

Et3N

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was sparged with N2 for 5 min
2. 2
   SonstigeThe mixture was sparged with N2 for 5 min
3. 3
   workup.ADDITIONThe mixture was diluted with EtOAc (200 mL)
4. 4
   Waschenwashed with 5% aq HCl (2×30 mL)
5. 5
   Trocknendried over Na2SO4
6. 6
   SonstigeRemoval of the solvent
7. 7
   workup.WAITleft a dark oil (379 mg) which
8. 8
   WaschenThe cartridge was eluted with 0, 25, 50 and 75% EtOAc in hexanes (20 mL) of each and EtOAc (2×20 mL)
9. 9
   Sonstigeto give six fractions
10. 10
    Einengenconcentrated

Vorschrift

A microwave vial was charged with (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (216 mg, 0.50 mmol), 3-hydroxy-3-methyl-1-butyne (0.24 mL, 2.50 mmol), CuI (9.5 mg, 0.05 mmol) and Et3N (4 mL). The mixture was sparged with N2 for 5 min and PdCl2(PPh3)2 (21 mg, 0.03 mmol) was added. The mixture was sparged with N2 for 5 min and heated at 100° C. for 2 h in the microwave. The mixture was diluted with EtOAc (200 mL), washed with 5% aq HCl (2×30 mL), satd aq NaHCO3 (30 mL) and brine (30 mL), and dried over Na2SO4. Removal of the solvent left a dark oil (379 mg) which was applied to a 2 g silica SPE Cartridge. The cartridge was eluted with 0, 25, 50 and 75% EtOAc in hexanes (20 mL) of each and EtOAc (2×20 mL) to give six fractions. Fractions 4 and 5 were pooled and concentrated to afford the title compound (193 mg, 89%) as an oil. LC-MS Method 1 tR=1.53 min, m/z=436, 378; 1H NMR (CDCl3) 1.12 (s, 3H), 1.18 (s, 3H), 1.52 (d, 3H), 1.60 (s, 6H), 2.15 (m, 1H), 2.19 (s, 2H), 2.20-2.45 (2H), 2.80 (m, 1H), 5.66 (q, 1H), 6.86 (d, 2H), 7.17 (d, 2H), 7.30-7.40 (5H)

Quelle