4-(Benzyloxy)-5-fluoro-1H-indole-2-carboxylic acid → 4-Benzyloxy-5-fluoro-1H-indole

HRID 1404073Notes

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]=1

Participants

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.

Workup

customreaction
temperatureThe reaction mixture was cooled
filtrationfiltered through Celite
washthe filter cake was washed with EtOAc
additiondiluted with water
extractionextracted three times with EtOAc
extractionThe organic extract
washwas washed with 1 N HCl, H2O and brine
dry with materialdried with NaSO4
concentrationconcentrated
customThe resulting residue was purified by column chromatography on silica gel eluting with EtOAc/hexanes

Sources & evidence

ORD record: ord-3c9ece307071472fb7f0f83f2fd67dbc
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912220B2

Reaction notes

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