4-(Benzyloxy)-5-fluoro-1H-indole-2-carboxylic acid → 4-Benzyloxy-5-fluoro-1H-indole
Reaction equation
[CH2:1]([O:8][C:9]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[C:12](C(O)=O)[NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Cu].C1(C2C=CC=CN=2)C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
4
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 235 °C
Procedure
Compound 1-4a (6.28 g, 0.022 mol), copper powder (7.05 g, 0.11 mol) and 2-phenylpyridine (50 mL) were heated at reflux (230-240° C.) under a stream of nitrogen for 10 min, by which time TLC analysis showed complete reaction. The reaction mixture was cooled, filtered through Celite, and the filter cake was washed with EtOAc. The filtrate and EtOAc washings were combined, diluted with water, and extracted three times with EtOAc. The organic extract was washed with 1 N HCl, H2O and brine, dried with NaSO4, and concentrated. The resulting residue was purified by column chromatography on silica gel eluting with EtOAc/hexanes to give the product as a greenish solid (1-5a) in 62% yield, 3.32 g. 1H NMR (300 MHz, CDCl3-d) δ (ppm) 5.31 (s, 2H), 6.62-6.64 (m, 1H), 6.93-7.03 (m, 2H), 7.15 (dd, 1H, J=3.0, 2.5), 7.31-7.40 (m, 3H), 7.49-7.52 (m, 2H), 8.12 (br, 1H). APCI [M+1]: 242.1.