Sodium Hydroxide → Benzyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate

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Reaction Steps

To a solution of 7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (14.70 g, 42.36 mmol) in glacial acetic acid (180 mL), add a solution of tin(II) chloride (25.0 g, 129.21 mmol) and tin(II) chloride dihydrate (19.5 g, 84.72 mmol) as a solution in 10% HCl (71 mL). Stir the resulting solution at room temperature for 24 h. TLC indicates an incomplete reaction. Add more tin(II) chloride dihydrate (49.3 g, 213.95 mmol) followed by 6M HCl (20 mL) and stir the reaction 24 h more at room temperature. TLC now shows complete reaction. Pour the reaction into a vigorously stirring solution of NaOH (135.4 g) in water (250 mL) with ice (500 mL) and EtOAc (600 mL). Stir the suspension vigorously for 10 min (pH=5) then add more NaOH (72 g) as a solution in water (100 mL). The suspension clears up on vigorous stifling for 1 h. Partition the layers (pH aq=9-10) and extract the aqueous with more EtOAc (2×600 mL). Dry the combined organics (K2CO3 and Na2SO4) and concentrate in vacuo. Dissolve the residue in methylene chloride and filter to remove residual inorganics. Remove the solvent in vacuo to give 13.38 g of 7-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as an oil.

Provenance & Evidence