2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → (4S,5R)-3-((E)-2-Methyl-hex-2-enoyl)-4,5-diphenyl-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A 20 L jacketed reactor was fitted with a reflux condenser. To the reactor was charged 1100 g (4.597 mol) of (4S,5R)-4,5-diphenyl-oxazolidin-2-one, 884 g (6.896 mol) (E)-2-methyl-2-pentenoic acid, 1705 g (6.896 mol) of EEDQ, 48 g (1.149 mol) of LiCl and 16 L of EtOAc. The reaction mixture was heated to 65° C. and was held for 200 minutes. The reaction mixture was cooled to room temperature and was extracted 3× with 3.5 L aliquots of 1N HCl. The combined aqueous extracts were filtered to give a white solid. The recovered white solid was added back to the organic layer. The 20 L reactor was fitted with a distillation head and the organic layer was distilled to remove in succession: 13.5 L of EtOAc, after which 5 L of heptane was added to the reactor; 5 L of EtOAc/heptane, after which 5 L of heptane was added to the reactor; and 2.7 L of EtOAc/heptane, after which 2.7L of heptane was added to the reactor. The contents of the reactor were cooled to 25° C. and the resulting mixture was filtered under 5 psig nitrogen while washing with 4 L of heptane. The wet cake was dried under nitrogen pressure overnight to give 1521 g of the titled compound: 1H NMR (DMSO) 7.12-6.94 (m, 8H), 6.834 (dd, 2H, J=7.813, 1.709), 6.060 (d, 1H, J=8.057), 6.050 (td, 1H, J=7.447, 1.221), 5.795 (d, 1H, J=8.057), 2.119-2.064 (m, 2H), 1.778 (d, 3H, J=0.997), 1.394 (m, 2H), 0.874 (t, 3H, J=7.324); Anal Calc'd for C22H23N1O3: C, 75.62; H, 6.63; N, 4.01. Found: C, 75.26; H, 6.72; N, 3.95.

Provenance & Evidence