Acetic Acid → Dimethyl indole-2,3-dicarboxylate

HRID 1912627Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8]([O:16][CH3:17])(=[O:15])[C:9]#[C:10][C:11]([O:13][CH3:14])=[O:12].C(O)(=O)C.O=O>CN(C)C(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH:1]1[C:2]2[C:7](=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]1[C:8]([O:16][CH3:17])=[O:15]

Participants

Conditions

Temperature: 115 °C

Procedure

A solution of aniline (3.91 ml, 43.0 mmol) and dimethyl but-2-ynedioate (5.28 ml, 43.0 mmol) in N,N-dimethylacetamide (DMA) (194 ml)/acetic acid (64.8 ml) was degassed with O2 for 5 min and treated with Pd(OAc)2 (0.964 g, 4.30 mmol). The reaction mixture was heated to 115° C. and placed under and atmosphere of O2. After 18 h, the reaction was cooled to ambient temperature, filtered through a pad of Celite™, diluted with EtOAc and washed with H2O. The organic was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by ISCO (0-50% EtOAc-hexanes: 220 g SiO2) to afford dimethyl 1H-indole-2,3-dicarboxylate (5.5 g, 23.58 mmol, 54.9% yield) as a yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ=9.32 (br. s., 1 H), 8.08 (d, J=8.2 Hz, 1 H), 7.48-7.44 (m, 1 H), 7.42-7.37 (m, 1 H), 7.29 (s, 1 H), 4.01 (d, J=2.0 Hz, 6 H); LCMS (m/z) ES+=234 (M+1).

Workup

temperaturethe reaction was cooled to ambient temperature
filtrationfiltered through a pad of Celite™
additiondiluted with EtOAc
washwashed with H2O
washThe organic was washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by ISCO (0-50% EtOAc-hexanes: 220 g SiO2)

Sources & evidence

ORD record: ord-240f4a4cf9cb41f29e4cbed1891e8b31
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609653B2

Reaction notes

Loading…