Sodium Chloride → 5-Bromo-7-fluoro-2,3-dihydro-1H-inden-1-one

HRID 520313Notes

Reaction equation

[Cl-].[Na+].[Cl-].[Cl-].[Cl-].[Al+3].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:18])[CH2:15][CH2:16]Cl)=[C:10]([F:19])[CH:9]=1>Cl>[Br:7][C:8]1[CH:13]=[C:12]2[C:11](=[C:10]([F:19])[CH:9]=1)[C:14](=[O:18])[CH2:15][CH2:16]2

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of sodium chloride (333 g, 5.69 mol) and aluminum trichloride (1270 g, 9.52 mol) was added to 144c (210 g, 0.79 mol) in several portions at 130° C. See FIG. 3. The neat reaction mixture was then stirred at 180° C. After 5 h the reaction mixture was poured into a stirred solution of ice water (1000 mL) and concentrated HCl (100 mL). The quenched reaction was stirred for 40 min and then extracted with DCM (4000 mL×3). The combined organic phase was washed with saturated NaHCO3 solution (1000 mL), brine (2000 mL×2), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE/EA=50/1, 10/1) to afford 55.0 g (30.4%) of 5-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one 144d. 1H NMR (400 MHz, CDCl3) δ 7.37 (s, 1H), 7.10-7.12 (d, J=8.4 Hz, 1H), 3.04-3.10 (m, 2H), 2.50-2.66 (m, 2H).

Workup

customThe quenched reaction
stirringwas stirred for 40 min
extractionextracted with DCM (4000 mL×3)
washThe combined organic phase was washed with saturated NaHCO3 solution (1000 mL), brine (2000 mL×2)
dry with materialdried with anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography (PE/EA=50/1, 10/1)

Sources & evidence

ORD record: ord-a432104909604e649bef4a2ca764e62f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09326985B2

Reaction notes

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