Hydrochloric Acid → 6-amino-2-(3-hydroxymethyl-phenyl)-1H-indole-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Intermediate 73(c) from Example 73 (1.8 g, 5 mmol) was dissolved in methanol (22 mL). 4M HCl in dioxane (22 mL, 75 mmol) was carefully added, and the solution was heated at 90° C. for 1 hour. After cooling to 22° C., the volatiles were removed in vacuo giving 6-amino-2-(3-hydroxymethyl-phenyl)-1H-indole-4-carboxylic acid methyl ester which was then combined with (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (2 g, 12.5 mmol), triethylamine (3.5 mL, 25 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (4.7 g, 12.5 mmol) in N,N-dimethylformamide (0.2 M, 25 mL) and stirred at 22° C. for 12 hours. Volatiles were removed in vacuo and the crude mixture dissolved in methanol (25 mL, 0.2 M) was treated with K2CO3 (1.38 g, 10 mmol) for 1 hour at 22° C. Excess K2CO3 was removed by filtration, and acetic acid (2 drops) was added to the filtrate. Following filtrate evaporation, the residue was subjected to silica gel chromatography (90:10 to 100:0 ethyl acetate/hexane) which provided Intermediate 85(a) (1.1 g, 2.5 mmol) in 50% yield.

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