Acetic Acid → Dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate

Participants

Reaction Steps

Stir a mixture of methyl 2-bromo-N-(methoxycarbonyl)-D-phenylalaninate (29.1 g, 92.10 mmol) and paraformaldehyde (9.13 g, 101.3 mmol) in glacial acetic acid (115 mL, 2.01 mol) and concentrated sulfuric acid (38.4 mL, 719.9 mmol) at room temperature for 7 hours. Partition between water and ethyl acetate. Separate the layers and extract the aqueous layer with ethyl acetate. Combine the ethyl acetate extracts and dry over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by silica gel chromatography eluting with ethyl acetate: hexanes (5-40% gradient) to give the title compound (27.6 g, 84.0 mmol). MS (m/z): 328 (M+1).

Provenance & Evidence