Tert-butyl 4-(methoxycarbonyl)-3-nitrobenzoate → 4-tert-butyl 7-methyl 1H-indole-4,7-dicarboxylate

HRID 906114Notes

Reaction equation

HRID 906114 reaction equation
[N+:1]([C:4]1[CH:13]=[C:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])([O-])=O.[CH:21]([Mg]Br)=[CH2:22]>O1CCCC1>[NH:1]1[C:4]2[C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=[C:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:13]=2[CH:22]=[CH:21]1

Participants

4

Reactant 2

HCID 23291046Tert-butyl 4-(methoxycarbonyl)-3-nitrobenzoateHCID 178418507HCID 178418507, compound

Product 1

HCID 674040144-tert-butyl 7-methyl 1H-indole-4,7-dicarboxylateYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-tert-butyl 1-methyl 2-nitroterephthalate (prepared according to Gao, Y. et. al WO2001070737) (2.15 g, 7.64 mmol) in tetrahydrofuran (30 mL) was added a 1M solution of vinylmagnesium bromide in tetrahydrofuran (23.0 mL) at −40° C., followed by stirring at room temperature for 18 hours. The reaction mixture was quenched by the addition of a solution of 1 M aqueous ammonium chloride, and the organic portion of the solvent was evaporated. The resulting material was partitioned with ethyl acetate (300 mL), and the organic layer was separated then washed with 10% aqueous citric acid (100 mL) and brine, dried over sodium sulfate, filtered and the solvent was concentrated. The resulting crude material was purified by column chromatography (hexane:ethyl acetate 9:1 to 7:3 eluent) to give 4-tert-butyl 7-methyl 1H-indole-4,7-dicarboxylate (0.58 g, 27%). 1H NMR (400 MHz, CDCl3): 10.00 (bs, 1H), 7.88 (dd, 2H), 7.43 (m, 1H), 7.19 (m, 1H), 4.00 (s, 3H), 1.66 (s, 9H). MS (EI) for C15H17NO4: 274 (M−H).

Workup

  1. customThe reaction mixture was quenched by the addition of a solution of 1 M aqueous ammonium chloride
  2. customthe organic portion of the solvent was evaporated
  3. customThe resulting material was partitioned with ethyl acetate (300 mL)
  4. customthe organic layer was separated
  5. washthen washed with 10% aqueous citric acid (100 mL) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe solvent was concentrated
  9. customThe resulting crude material was purified by column chromatography (hexane:ethyl acetate 9:1 to 7:3 eluent)

Sources & evidence

ORD record
ord-60b442cc47364669b2a300eb240a9895
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

Loading…