dimethyl 3-amino-4-hydroxybenzene-1,2-dicarboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3-amino-4-hydroxyphthalate C1-4 (11.25 g, 50 mmol) and NaOH (14.0 g, 350 mmol) in ethanol (140 mL) and H2O (50 mL) was stirred at 70° C. overnight. LCMS indicated that the reaction was complete. The reaction mixture was concentrated in vacuo, neutralized to pH<3, and filtered to yield 3-amino-4-hydroxyphthalic acid C1-5 as a white solid (9.6 g, yield: 97%), which was used directly in the next step without further purification. The reaction mixture was concentrated in vacuo filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the crude dimethyl 4-hydroxy-3-nitrophthalate C1-3 (25 g, 98 mmol) and Pd/C (1.0 g) in CH3OH (400 mL) was stirred at room temperature overnight under H2 atmosphere. LCMS showed that the reaction was complete. The reaction mixture was filtered through a celite pad and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica gel, PE:EA (1:1, v:v)) to yield compound C1-4 as a yellow solid (11.5 g, yield: 52%). 1H NMR (DMSO-d6, 400 MHz) δ: 10.45 (s, 1H), 6.89 (d, J=8 Hz, 1H), 6.37 (d, J=8 Hz, 1H), 5.19 (s, 2H), 3.75 (s, 3H), 3.72 (s, 3H); MS (ESI+): m/z 226 (M+1). The reaction mixture was filtered through a celite pad the filtrate was evaporated in vacuo The residue was purified by chromatography (silica gel, PE:EA (1:1, v:v))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the crude dimethyl 4-hydroxy-3-nitrophthalate C1-3 (25 g, 98 mmol) and Pd/C (1.0 g) in CH3OH (400 mL) was stirred at room temperature overnight under H2 atmosphere. LCMS showed that the reaction was complete. The reaction mixture was filtered through a celite pad and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica gel, PE:EA (1:1, v:v)) to yield compound C1-4 as a yellow solid (11.5 g, yield: 52%). 1H NMR (DMSO-d6, 400 MHz) δ: 10.45 (s, 1H), 6.89 (d, J=8 Hz, 1H), 6.37 (d, J=8 Hz, 1H), 5.19 (s, 2H), 3.75 (s, 3H), 3.72 (s, 3H); MS (ESI+): m/z 226 (M+1). The reaction mixture was filtered through a celite pad the filtrate was evaporated in vacuo The residue was purified by chromatography (silica gel, PE:EA (1:1, v:v))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of dimethyl 3-nitro-4-hydroxyphthalate (28.9 g, 0.113 mol), ethanol and 5% platinum on carbon (2.80 g, 50% aqueous) is shaken on a Parr hydrogenator under hydrogen for 1.75 hours at room temperature. The reaction mixture is filtered through diatomaceous earth and the filtrate is concentrated in vacuo to give a pale green solid residue. Chromatography (silica gel, ethyl acetate:methylene chloride eluent) affords the title product as a pale yellow solid, 3.69 g, mp 112°-113° C., identified by NMR and IR spectral analyses. The reaction mixture is filtered through diatomaceous earth the filtrate is concentrated in vacuo to give a pale green solid residue