Cesium carbonate → Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 1625018Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[C:9]([I:15])=[CH:10][C:11](=[O:14])[NH:12][CH:13]=1.Br[CH2:17][CH2:18][C@@:19]([CH3:29])([S:25]([CH3:28])(=[O:27])=[O:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21]>C1COCC1>[F:7][C:8]1[C:9]([I:15])=[CH:10][C:11](=[O:14])[N:12]([CH2:17][CH2:18][C@@:19]([CH3:29])([S:25]([CH3:28])(=[O:27])=[O:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:13]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Cesium carbonate (1.77 g, 5.44 mmol) was added to a suspension of 5-fluoro-4-iodopyridin-2(1H)-one (1.00 g, 4.2 mmol) and ethyl (2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate (1.56 g, 5.44 mmol) in anhydrous THF (45 mL). The reaction was heated to 70° C. and stirred at this temperature overnight. The reaction was quenched with water (100 mL) and extracted with EtOAc (2×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered, and concentrated. The crude product was purified via flash chromatography using a Varian SF15-24 g column and an eluent of EtOAc in n-heptane (30-80%) to afford the title compound as a yellow residue (691 mg, 37%). MS (LCMS) m/z 446.0 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (t, 3 H) 1.75 (s, 3 H) 2.37-2.57 (m, 2 H) 3.10 (s, 3 H) 3.83-4.02 (m, 1 H) 4.16-4.37 (m, 3 H) 7.15 (d, 1 H) 7.20 (d, J=3.32 Hz, 1 H).

Workup

customThe reaction was quenched with water (100 mL)
extractionextracted with EtOAc (2×100 mL)
washThe combined organics were washed with brine (100 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified via flash chromatography

Sources & evidence

ORD record: ord-793813d657d14798920ec34b97d8b787
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08779148B2

Reaction notes

Loading…