[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH:15]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:24][C:25](=O)[CH:26](Br)[CH2:27]C)C.COCCCC.C[O-].[Na+]>O.C(O)(=O)C>[CH2:26]([C:25]([CH2:15][C:14]1[CH:17]=[CH:18][C:19]([O:20][CH3:21])=[C:12]([O:11][CH2:10][CH2:9][O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:13]=1)=[O:24])[CH3:27]24 g of the product of step (ii) 21.5 g bromobutyric acid ethyl ester and 30 ml t.butyl methyl ether are added dropwise over 50 mins. at 5° C. to a pre-prepared suspension of sodium methylate in 25 ml t.butyl methyl ether. The reaction mixture is stirred for 45 mins. at ca. 5° C. and then stirred for 12 hrs. at room temperature. The pH is adjusted to 5 by addition of glacial acetic acid and the obtained suspension diluted with H2O and extracted 3× with t.butyl methyl ether. The organic phase is extracted with NaHCO3 (1×) and brine (1×), and evaporated to ca. 100 ml. 13.5 ml 50% aqueous NaOH are added drop-wise and the whole stirred for 2 hrs. at 40° C., diluted with 50 ml. H2O and stirred for a further 30 mins. at room temperature. The organic phase is separated and the aqueous phase adjusted to pH 1 at max. 40° C. with 15 ml conc. HCl. The reaction mixture is stirred at 40° C. for a further 1.5 hrs., cooled to room temperature and extracted with toluene. The organic phase is washed with NaHCO3 and brine, dried over Na2SO4, filtered and evaporated to yield the title compound as an oil.
読み込み中…
