Benzyl Bromide → Indole-2-carboxylic acid, 1-benzyl-, ethyl ester

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

Procedure

To a solution of 1H-indole-2-carboxylic acid ethyl ester (1.89 g, 10.0 mmol) and benzylbromide (1.71 g, 10.0 mmol) in acetone (50 mL) was added cesium carbonate (3.26 g, 10.0 mmol). The mixture was heated to reflux overnight and then allowed to cool back to room temperature. The mixture was partitioned between ethyl acetate and brine and the layers were then separated. The aqueous layer was extracted with one additional portion of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (0/100 gradient to 6/94) to give 1-benzyl-1H-indole-2-carboxylic acid ethyl ester (2.38 g, 85%) as a white solid. 1H NMR (400 MHz, CDCl3); δ 7.68 (d, 1H), 7.37-7.11 (m, 7H), 7.02 (d, 2H), 5.82 (s, 2H), 4.30 (q, 2H), 1.33 (t, 3H).