Methanesulfonic Acid → 6-Fluoro-1,2,3,4-tetrahydroisoquinolin-1-one

HRID 1772274Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.CS(O)(=O)=O.[N-:17]=[N+]=[N-].[Na+]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:17][CH2:6][CH2:5]2

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-fluoro-2,3-dihydro-1H-inden-1-one (4.5 g, 29.97 mmol) in dichloromethane (50 ml) was added methanesulfonic acid (40 ml). This was followed by the addition of sodium azide (2.73 g, 42.0 mmol) in several batches with stirring over 2 hours at 0° C. The reaction mixture was then quenched with aqueous sodium hydroxide and extracted with dichloromethane (2×100 ml). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue, which was purified by silica gel column chromatography using 10%-100% ethyl acetate in petroleum ether to afford 6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-one as a white solid (2.5 g, 51%); (ES, m/z): [M+H]+ 166; 1H NMR (300 MHz, CDCl3): δ 8.11 (dd, J=6.0, 8.7 Hz, 1H), 7.07-7.00 (m, 1H), 6.94 (dd, J=2.4, 8.7 Hz, 1H), 6.57 (br s, 1H), 3.61 (t, J=6.6, 2H), 3.03 (t, J=6.6, 2H).

Workup

customThe reaction mixture was then quenched with aqueous sodium hydroxide
extractionextracted with dichloromethane (2×100 ml)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customto give a residue, which
customwas purified by silica gel column chromatography

Sources & evidence

ORD record: ord-398536923a3648e0907e176956116596
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249102B2

Reaction notes

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