Réaction #792229

Équation de réaction

sodium hydroxide

methyl 1-oxo-1,2-dihydroisoquinoline-4-carboxylate

hydrogen

methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate

→

1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid

Rendement 94.0%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autrewas hydrogenated at 70° C.
2. 2
   Filtrationafter which the catalyst was filtered off
3. 3
   Autrethe solvent was removed under reduced pressure
4. 4
   Autrethe crude product was purified by chromatography (ethyl acetate: n-heptane 2:1)
5. 5
   Autrethe solvent was removed under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
7. 7
   AutreThe phases were separated
8. 8
   Séchagethe organic phase was dried over magnesium sulphate
9. 9
   Autrethe solvent was removed under reduced pressure

Mode opératoire

2.50 g (12.30 mmol) of methyl 1-oxo-1,2-dihydroisoquinoline-4-carboxylate and 1.30 g of 10% strength palladium on carbon were suspended in an autoclave, and the mixture was hydrogenated at 70° C. and 20 bar of hydrogen for 4 h. The autoclave was vented, after which the catalyst was filtered off and the solvent was removed under reduced pressure, and the crude product was purified by chromatography (ethyl acetate: n-heptane 2:1). This gave 2.28 g (88%) of the desired methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate. 1H-NMR (400 MHz, CDCl3 δ, ppm) 8.10 (d, 1H), 7.52 (t, 1H), 7.44 (t, 1H), 7.31 (d, 1H), 6.17 (br. s, 1H), 3.98 (dt, 1H), 3.88 (m, 1H), 3.29 (dd, 1H), 3.71 (s, 3H). 2.28 g (11.11 mmol) of methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate were dissolved in 20 ml of tetrahydrofuran, and 20 ml of 1 N aqueous sodium hydroxide solution were added. The solution was stirred at room temperature for 8 h, the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and 1 N hydrochloric acid. The phases were separated, the organic phase was dried over magnesium sulphate and the solvent was removed under reduced pressure. In this manner, 2.12 g (94% of theory) of the desired 1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid were obtained. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 12.65 (br. s, 1H), 7.94 (d, 1H), 7.83 (d, 1H), 7.51 (t, 1H), 7.41-7.35 (m, 2H), 3.89 (t, 1H), 3.68-3.54 (m, 2H). 0.200 g (1.046 mmol) of 1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid were dissolved in 10 ml of acetonitrile, and 0.109 ml (1.569 mmol) of cyclopropylamine, 0.170 g (1.255 mmol) of 1-hydroxy-1H-benzotriazole and 0.221 g (1.151 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. The solution was stirred at room temperature for 8 h, diluted with ethyl acetate and the organic phase was extracted initially with saturated sodium bicarbonate solution and then with 1 N hydrochloric acid.

Source