5-Bromo-2-chloroanisole → HCID 10295422, compound

Participants

Reaction Conditions

Reaction Steps

A quantity of 0.85 g (3.0 mmoles, 1 eq) of 6-(3,4-dimethoxy-phenyl)-octahydro pyrido[1,2-a]pyrazine and 0.76 g (3.4 mmoles, 1.1 eq) of 5-bromo-2-chloro-anisole is dissolved in 25 mL of anhydrous toluene, and the solution is purged with N2 for 20 min. To the solution is added 0.18 g (0.30 mmoles, 0.10 eq) of rac-2,2′-Bis(diphenyl-phosphino)-1,1′-binapphtyl, 0.14 g (0.15 mmole, 0.05 eq) of Tris(dibenzylideneacetone)-dipalladium(0) and 0.52 g (4.6 mmoles, 1.5 eq) of Potassium tert-butoxide in order. The mixture is heated at 80° C. under N2 overnight. After it is cooled down, the reaction is filtered through Celite. The organic solution is washed with 1N NaOH and brine, dried over Na2SO4 and concentrated. The residue is purified by flash chromatography on silica gel eluted with 50:1 dichloromethane:methanol to afford 2-(4-chloro-3-methoxy-phenyl)-6-(3,4-dimethoxyphenyl)-octahydro-pyrido[1,2-a]pyrazine (compound 5) as a brownish stick solid (0.85 g, 68%). Analysis: 1H NMR (300 MHz, CDCl3): 7.16 (1H, d), 6.80 (3H, m), 6.40 (2H, m), 3.88 (3H, s), 3.86 (3H, s), 3.85 (3H, s), 3.40 (2H, m), 2.95 (1H, m), 2.70 (3H, m), 2.30 (1H, m), 2.00 (1H, m), 1.82-1.40 (6H, m). MS (LC-MS): Calculated for C23H29ClN2O3 416.94, found 417.23 (M+1). X. (6R,9S) 2-(4-chloro-3-methoxy-phenyl)-6-(3,4-dimethoxy-phenyl)-octahydro-pyrrolo[1,2-a]pyrazin via Scheme J

Provenance & Evidence