Sodium Hydroxide → HCID 9936657, compound

Participants

Reaction Steps

To a suspension of lithium aluminium hydride (1.2 g) in THF (50 mL) was added a solution of (3R,6R,8aR)-3-(1H-Indol-3-ylmethyl)-1,4-dioxo-octahydro-pyrrolo[1,2-a]pyrazine-6-carboxylic acid ethyl ester (1.75 g) in THF (50 mL). The resulting mixture was heated under reflux for 3 hours, then a mixture of water (3 mL) and THF (30 mL) was added drop-wise followed by 50% sodium hydroxide (aq, 0.5 mL), and heating under reflux was continued for 2 hours. After cooling to room temperature diisopropylethylamine (4 mL) and 3,5-bis(trifluoromethyl)benzoyl chloride (2.4 mL) were added and stirring was continued overnight. Ethyl acetate was added and the mixture extracted with sodium bicarbonate (5% aq. soln.). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 95:4.5:0.5) to afford 3,5-bis(trifluoromethyl)phenyl-[(3R,6R,8aR)-6-hydroxymethyl-3-(1H-indol-3-ylmethyl)-hexahydropyrrolo[1,2-a]pyrazin-2-yl]-methanone (1.49 g). MH+ 526; Rf 0.20 (EtOAc) (compound 1).

Provenance & Evidence