A solution of the dianion of butyric acid (5.6 mmol) [prepared from butyric acid (5.6 mmol) and lithium di-isopropylamide (5.6 mmol) in tetrahydrofuran (THF) (30 ml) and dimethylpropyleneurea (11.2 mmol)]was added to a solution of methyl 4-[5-formyl-1-propylindol-3-ylmethyl]-3-methoxybenzoate (2.0 g) in THF (15 ml) cooled in an ice-bath, under a nitrogen atmosphere, at such a rate as to maintain the temperature of the reaction below 10°. The mixture was allowed to warm to room temperature, stirred for an additional hour, poured into 20% (w/v) citric acid solution (150 ml), and extracted with ethyl acetate. The organic extracts were washed (water (twice), brine), dried (MgSO4) and evaporated to give a yellow oil. The product was purified by flash chromatography, eluting with 80:20:2 toluene:ethyl acetate:acetic acid, to give methyl 4-[5-(2-carboxy-1-hydroxybutyl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate (1.25 g, 48%, as a separable mixture of diastereomers), as a foam; isomer A partial NMR (300 Mz, DMSO-d6): 0.66(t, 3H, CH3), 0.81 (t, 3H, CH3), 3.83(s, 3H, OCH3), 3.92(s, 3H, OCH3), 4.53(d, 1H, CHOH), 5.23(br s, 1H, CHOH); isomer B partial NMR (300 Mz, DMSO-d6): 0.85(m, 6H, 2×CH3), 3.83(s, 3H, OCH3), 3.92(s, 3H, OCH3), 4.62(d, 1H, CHOH), 5.20(br s, about 1H, CHOH).
