Water → 1-(6-Fluoropyridin-3-yl)-4-oxocyclohexane-1-carbonitrile

HRID 512148Notes

Reaction equation

COC([C:5]1[CH2:10][C:9]([C:18]#[N:19])([C:11]2[CH:12]=[N:13][C:14]([F:17])=[CH:15][CH:16]=2)[CH2:8][CH2:7][C:6]=1[OH:20])=O.[Na+].[Cl-].O>CS(C)=O>[F:17][C:14]1[N:13]=[CH:12][C:11]([C:9]2([C:18]#[N:19])[CH2:8][CH2:7][C:6](=[O:20])[CH2:5][CH2:10]2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 5-Cyano-5-(6-fluoro-pyridin-3-yl)-2-hydroxy-cyclohex-1-enecarboxylic acid methyl ester (32 g crude, 0.11 mmol) in DMSO (110 mL) was added NaCl (7.78 g, 0.133 mol) and water (6.5 mL). The reaction mixture was heated at 160° C. for 3 h. It was cooled to room temperature and poured into water (300 mL). The aqueous layer was extracted with EtOAc (3×200 mL). The combined organic layer was washed with brine (300 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (eluting with a gradient elution of between 10-25% EtOAc in petroleum ether) to give the title compound (12 g, 50% over two steps). 1H NMR (CDCl3 400 MHz): ppm 8.34 (d, J=2.4 Hz, 1H), 7.95-7.82 (m, 1H), 7.00-6.92 (m, 1H), 2.95-2.87 (m, 2H), 2.60-2.2. (m, 2H), 2.50-2.40 (m, 2H), 2.28-2.20 (m, 2H).

Workup

temperatureIt was cooled to room temperature
extractionThe aqueous layer was extracted with EtOAc (3×200 mL)
washThe combined organic layer was washed with brine (300 mL)
dry with materialdried over sodium sulphate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by flash column chromatography on silica gel (
washeluting with a gradient elution of between 10-25% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-c27da34e316845c783c377f0ab141af9
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102591B2

Reaction notes

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