Hydrochloric Acid → (R)-7-(8-Hydroxy-2,3-diphenyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

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Reaction Steps

To a solution of (R)-ethyl 7-(8-acetoxy-2,3-diphenyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (step 1) (24.4 mg, 0.049 mmol) in THF (3 ml) and water (1 ml) was added LiOH (6.99 mg, 0.292 mmol). The reaction mixture was heated to reflux for 1.5 h. A further 6 equivalents of LiOH was added and heated continued at reflux for 1 h. After cooling to RT, the pH of the mixture was adjusted to pH below 5 by addition of 2M HCl. The volatile solvent was removed in vacuo. To the residue was added water (10 ml) and the mixture was extracted with ethyl acetate (3×10 ml). The organic phase were combined, dried over MgSO4, filtered and concentrated in vacuo. Purification of the crude product was carried out by chromatography on silica eluting with 0-100% EtOAc/iso-hexane followed by 0-100% MeOH/DCM. The residue was passed through a pre-conditioned Isolute SCX-2 SPE column loading with MeOH and eluting with 1M ammonia in MeOH. The basic fraction was concentrated in vacuo and the residue was dissolved in THF (3 ml) and water (1.0 ml) and treated with LiOH (6.99 mg, 0.292 mmol). After stirring at reflux for 1.5 h, the mixture was allowed to cool to RT and acidifed with 2M HCl to pH below 5. The volatile solvent was removed in vacuo. To the residue was added water (10 ml) and the mixture was extracted with ethyl acetate (3×10 ml). The organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound;

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