[H-].[Na+].[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[CH2:21][CH2:20][C:15]3([O:19][CH2:18][CH2:17][O:16]3)[CH2:14][CH:13]2[OH:22])=[C:8](F)[C:7]=1[F:24])[CH3:4].O.Cl>CCCCC.C1(C)C=CC=CC=1.CN(C=O)C>[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]2[CH:12]3[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14][CH:13]3[O:22][C:8]=2[C:7]=1[F:24])[CH3:4]
50.0 g (1.25 mol) of sodium hydride (60% suspension in mineral oil) are washed repeatedly with n-pentane and suspended in 3000 ml of toluene. The suspension is heated to 90° C., and a solution of 145.0 g (0.46 mol) of 8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol in 700 ml of DMF is slowly metered in. The batch is stirred at 90° C. for 30 h, cooled and hydrolysed using water. The mixture is neutralised by addition of 2 N hydrochloric acid, and the organic phase is separated off. The aqueous phase is extracted with toluene, and the combined organic phases are washed with sat. sodium chloride solution. The solution is dried using sodium sulfate and concentrated to dryness under reduced pressure. The crude product obtained is recrystallised from ethanol at 5° C., giving (±)-(4aR*, 9bS*)-7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-spiro-[dibenzo[b,d]-furan-3,2′-1,3-dioxolane] as colourless solid.
Wird geladen…
