Hydrochloric Acid → HCID 54521811, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-benzyl-7-bromo-1,2,3,4-tetrahydro-quinoxaline-1-carboxylic acid tert-butyl ester (2.4 g, Reference Example 5), tri-o-tolylphosphine (96 mg), palladium(II) acetate (24 mg) and ethyl acrylate (1.3 ml) in tributylamine (20 ml) was heated to 110° C. After stirring for 2 hours at 110° C. the mixture was treated with further portions of ethyl acrylate (1.3 ml), tri-o-tolylphosphine (96 mg) and palladium(II) acetate (24 mg) and stirring was continued for a further 16 hours at 110° C. The mixture was then treated with ethyl acrylate (2.6 ml) and stirring was continued for a further 5 hours at 110° C. The reaction mixture was cooled to room temperature then acidified to pH 2 by addition of hydrochloric acid (50 ml, 1N) and then extracted three times with ethyl acetate (50 ml). The combined organic extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate (20 ml), then three times with water (20 ml), then dried over magnesium sulphate and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting brown oil (5 g) was subjected to flash chromatography on silica (0,040-0,063 mm) eluting with a mixture of cyclohexane and ethyl acetate (9:1, v/v) to give the title compound (1.83 g) as a yellow oil. 1H NMR, 400 MHz, (CD3)2SO: δ1.3 (t, 3H); 1.5 (s, 9H); 3.5 (broad t, 2H); 3.8 (broad t, 2H); 4.15 (q, 2H); 4.65 (s, 2H); 6.25 (d, J=16 Hz, 1H); 6.65 (d, J=8 Hz, 1H); 7.3 (m, 4H); 7.4 (t, 2H); 7.5 (d, J=16 Hz, 1H); 7.7 (broad s, 1H). MS (EI): M+ 422 (50%), 366 (60%), 322 (40%), 277 (20%), 231 (40%), 185 (10%), 157 (15%), 91 (100%), 57 (40%).

Provenance & Evidence