2,2-Dimethyl-1,3-dioxane-4,6-dione → 2-Hydroxy-4-(2-oxo-6-phenyl-5-(thiophen-3-yl)-1,2,3,4-tetrahydropyridin-4-yl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-phenyl-2-(thiophen-3-yl)ethanone (Intermediate 6) (300 mg, 1.5 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 5) (325 mg, 1.8 mmol), meldrum's acid (260 mg, 1.8 mmol) and AcONH4 (140 mg, 1.8 mmol) in AcOH (3 mL) was refluxed overnight. The mixture was concentrated in vacuo and the residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 40° C. overnight. The resulting mixture was cooled to room temperature, and then acidified with aq. HCl (2 M, 12 mL) to pH=5. Followed a standard aqueous/EtOAc workup i.e. the mixture was extracted with EtOAc (3 times), washed with brine, then combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound 7 (25 mg, 2-steps yield 4%) as yellow solid. 1H NMR (DMSO-d6 400 MHz): δ 9.60 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.44-7.36 (m, 3H), 7.35-7.26 (m, 3H), 7.22-7.15 (m, 1H), 7.14-6.98 (m, 2H), 6.82-6.74 (m, 1H), 6.25 (d, J=4.8 Hz, 1H), 4.13-4.05 (m, 1H), 3.18 (dd, J=16.2, 8.0 Hz, 1H), 2.46-2.42 (m, 1H). MS (ESI): m/z 391.7 [M+1]+.

Provenance & Evidence