Formaldehyde → (3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester

Participants

Reaction Steps

(S)-3-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester (1.0 g) was dissolved in 37 mL dry dioxane and 149 mg paraformaldehyde added. 30 mL dry dioxane and 17 mL trifluoroacetic acid were mixed, cooled on ice and added to the reaction mixture. The reaction was stirred for 20 hours at room temperature and diluted with EtOAc. The organic layer was washed with 10% sodium, dried over Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (DCM+0.2% TEA) to give 934 mg of product after drying. 1H NMR (400 MHz, acetone-d6): 7.71 (d, 1H), 7.61 (d, 1H), 7.50-7.41 (m, 3H), 7.38-7.26 (m, 5H), 7.09 (m, 2H), 6.67 (s, 1H), 6.60 (s, 1H), 5.19 (s, 2H), 5.10 (m, 1H), 4.32 (m, 1H), 4.12 (m, 2H), 4.01 (m, 1H), 3.92 (m, 1H), 3.59 (m, 1H), 3.51 (s, 3H), 2.97-2.78 (m, 2H), 2.16 (m, 1H), 1.68 (m, 1H), 0.66 (t, 3H).

Provenance & Evidence