A Practical and Cost-Effective Synthesis of 6,7-Dimethoxy-2-tetralone

Abstract

The cyclic ketone, 6,7-dimethoxy-2-tetralone, a versatile starting material for many dopaminergic compounds, can be prepared practically, cost-effectively and in good overall yield. The synthesis starts from readily available 3,4-dimethoxyphenylacetic acid. Ring iodination gave the 2-iodo-4,5-dimethoxy acid, which was converted to its methyl ester. Palladium (II)-catalyzed Heck cross coupling afforded the expected unsaturated diester, which was then catalytically hydrogenated. Dieckmann condensation, followed by careful decarboxylation led to the desired 2-tetralone. Reagents used in subsequent reactions are inexpensive and readily available. This method appears practical for large-scale synthesis of the target tetralone, compared with other procedures reported in the literature.

Probing the Steric Space at the Floor of the D1 Dopamine Receptor Orthosteric Binding Domain: 7α-, 7β-, 8α-, and 8β-Methyl Substituted Dihydrexidine Analogues

“…Intramolecular Dieckmann condensation gave an intermediate ketoester that was decarboxylated by treatment with lithium chloride and HCl in boiling N -methylpyrrolidinone. Treatment of the resulting β-tetralone 9 with benzylamine, followed by benzoyl chloride gave access to enamide 10 , which was irradiated using a 450W medium-pressure, quartz mercury-vapor lamp to induce cyclization, 19–21 giving a 50/50 mixture of the α- and β-methyl trans- lactams 11 in moderate yield. Chromatographic separation of this mixture allowed isolation of small amounts of pure axial β-methyl lactam 11a (Scheme 2).…”

Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D3 receptor-selective full agonist ligand

“…12 Treatment of 6 with pyrrolidine gave the corresponding enamide, which underwent Stork-Ninomiya aza-annulation in the presence of acrylamide to give amide 7 . 13,14 Reduction of 7 with Et 3 SiH/TFA to lactam 8 was successful only in the presence of ZnCl 2 , affording exclusively the desired trans lactam 8 in excellent yield.…”

Regio- and Stereoselective Electrophilic Cyclization Approach for the Protecting-Group-Free Synthesis of Alkaloids Lennoxamine, Chilenine, Fumaridine, 8-Oxypseudoplamatine, and 2-O-(Methyloxy)fagaronine

“…This compound was prepared by following the same procedure as synthesis of 10 . Methyl 2-(2-iodo-4,5-dimethoxyphenyl)­acetate (2.17 g, 6.46 mmol) and ethynyltrimethylsilane (0.761 g, 7.75 mmol, 1.2 equiv) afforded methyl 2-(4,5-dimethoxy-2-((trimethylsilyl)­ethynyl)­phenyl)­acetate (1.96 g, 99%) as a yellow oil: 1 H NMR (400 MHz, CDCl 3 ) δ 6.93 (s, 1H), 6.74 (s, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.75 (s, 2H), 3.68 (s, 3H), 0.22 (s, 9H); IR (neat) 2956, 2844, 2148, 1740, 1513 cm –1 ; HRMS (ESI-TOF) m / z [M + H] + calcd for C 16 H 22 O 4 Si 307.1360, found 307.1377. 2-(4,5-Dimethoxy-2-((trimethylsilyl)­ethynyl)­phenyl)­acetate (1.56 g, 5.09 mmol) afforded methyl 2-(2-ethynyl-4,5-dimethoxyphenyl)­acetate ( 20 ) (1.14 g, 96%) as a light yellow solid: mp 89–90 °C; 1 H NMR (400 MHz, CDCl 3 ) δ 6.96 (s, 1H), 6.76 (s, 1H), 3.87 (s, 3H), 3.84 (s, 3H), 3.78 (s, 2H), 3.69 (s, 3H), 3.18 (s, 1H); 13 C­{ 1 H} NMR (101 MHz, CDCl 3 ) δ 171.9, 150.0, 148.0, 130.2, 115.2, 114.5, 112.8, 82.1, 80.2, 56.2, 56.2, 52.2, 39.3; IR (neat) 3237, 1720, 1514, 1453, 1332 cm –1 ; HRMS (ESI-TOF) m / z [M + H] + calcd for C 13 H 14 O 4 235.0965, found 235.0965.…”