Methanol → HCID 71209434, compound

An ice cold solution of dimethyl 1H-indole-2,3-dicarboxylate (3 g, 12.86 mmol) in N,N-dimethylformamide (DMF) (31.5 ml) was treated with NaH (0.617 g, 15.44 mmol) and methyl iodide (0.881 ml, 14.15 mmol) and warmed to 75° C. After 8 h, the reaction mixture was partitioned between EtOAc and sat. aq. NH4Cl. The combined organics were washed with water (3×), brine, dried (MgSO4), filtered and concentrated. The residue was treated with a solution of KOH (8.66 g, 154 mmol) in EtOH (200 mL) and heated to reflux (95° C. bath temp). After 8 h, the reaction mixture was cooled to ambient temperature, diluted with EtOAc and the layers partitioned. The aqueous layer was extracted with EtOAc (2×) and acidified with 1 M HCl to pH 3. The aqueous layer was then extracted with EtOAc and the organics were washed with brine, dried (MgSO4), filtered and concentrated to afford 1-methyl-1H-indole-2,3-dicarboxylic acid (2.82 g, 12.87 mmol, 100% yield) as a white solid. The acid was suspended in DCM (30 mL) and treated dropwise with TFAA (4.39 ml, 32.2 mmol). After 2 h, the reaction mixture was concentrated in vacuo to afford 4-methyl-1H-furo[3,4-b]indole-1,3(4H)-dione as a purple solid. The anhydride was suspended in MeOH (100 mL) and stirred at ambient temperature. After 18 h, the reaction mixture was concentrated in vacuo to afford 3-(methoxycarbonyl)-1-methyl-1H-indole-2-carboxylic acid (2.95 g, 12.65 mmol, 98% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ=8.00 (s, 1 H), 7.64 (d, J=8.4 Hz, 1 H), 7.40-7.33 (m, 1 H), 7.28 (s, 1 H), 3.82 (d, J=5.7 Hz, 6 H); LCMS (m/z) ES+=234 (M+1).

1. concentrationthe reaction mixture was concentrated in vacuo

ORD record

ord-0f38bf2763eb4f72999be7a93b053e42

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609653B2