Potassium Carbonate → HCID 58763428, compound

HRID 858285Notes

Reaction equation

HRID 858285 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:2].[CH3:21][O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O.[Cu]Br>[CH2:18]([O:17][C:15]([C:7]1[N:8]([C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([C:23]([O:22][CH3:21])=[O:31])[CH:25]=2)[C:9]2[C:14]([C:6]=1[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:20])=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:16])[CH3:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 12070Methyl 3-bromobenzoateHCID 11821846HCID 11821846, compound

Product 1

HCID 58763428HCID 58763428, compoundYield 73.3%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (2-ethoxycarbonyl-indol-3-yl)-acetic acid ethyl ester (J. Med. Chem. 1991, 34, 1283–1292, 2.2 g, 8.0 mmol), methyl-3-bromobenzoate (5.16 g, 24 mmol), anhydrous powdered K2CO3 (2.2 g, 16 mmol), and copper (I) bromide (2.3 g, 16 mmol) in N-methylpyrrolidone (NMP, 10 mL) was stirred at 170° C. overnight under inert atmosphere. The solvent was then removed by stream of nitrogen, and the residue was suspended in EtOAc (20 mL). The suspension was passed through a pad of silica gel using EtOAc-hexanes (1:2) as an eluent. The filtrate was concentrated in vacuo and purified by HPLC on LUNA 10μ silica column 25×250 mm with RI detector to afford 2.4 g of 3-ethoxycarbonylmethyl-1-(3-methoxycarbonyl-phenyl)-1H-indole-2-carboxylic acid ethyl ester as a white solid (73% yield): 1H NMR (CDCl3) δ 1.11 (t, J=7.3 Hz, 3H), 1.27 (t, J=7.1 Hz, 3H), 3.91 (s, 3H), 4.12–4.24 (m, 6H), 7.01–7.06 (m, 1H), 7.17–7.32 (m, 2H), 7.51–7.62 (m, 2H), 7.69–7.75 (m, 1H), 8.01–8.04 (m, 1H), 8.11–8.14 (m, 1H).

Workup

  1. customThe solvent was then removed by stream of nitrogen
  2. concentrationThe filtrate was concentrated in vacuo
  3. custompurified by HPLC on LUNA 10μ silica column 25×250 mm with RI detector

Sources & evidence

ORD record
ord-6d746aa6cf16494dbd9dd59abbe89651
Source dataset
uspto-grants-2006_12
Patent number
US07148250B2

Reaction notes

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