Potassium Phosphate, Tribasic → 5-(5-Ethylsulfonyl-2-fluorophenyl)-3-methoxy-1-methylpyridin-2-one

HRID 575814Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH2:12]([S:14]([C:17]1[CH:18]=[CH:19][C:20]([F:32])=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=1)(=[O:16])=[O:15])[CH3:13].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:12]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([F:32])=[C:19]([C:2]2[CH:3]=[C:4]([O:10][CH3:11])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH:18]=1)(=[O:15])=[O:16])[CH3:13]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 5-bromo-3-methoxy-1-methylpyridin-2-one (694 mg, 3.18 mmol), 2-(5-ethylsulfonyl-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1 g, 3.18 mmol), Pd(dppf)Cl2 (233 mg, 318.00 umol) in dioxane (26 mL) and H2O (2.6 mL) was added K3PO4 (2.02 g, 9.54 mmol, 3.00 Eq). The reaction was stirred at 70° C. under N2 for 6 hrs. The mixture was concentrated and the residue was purified by silica gel column chromatography (PE/EA=3/1 to 1/2) to afford the title compound (0.9 g, 87%) as a brown solid. 1H NMR (CDCl3, 400 MHz) δ 7.93 (dd, J1=7.2 Hz, J2=2.0 Hz, 1H), 7.88-7.84 (m, 1H), 7.35 (dd, J1=10.0 Hz, J2=8.8 Hz, 1H), 7.23 (d, J=1.6 Hz, 1H), 6.83 (s, 1H), 3.89 (s, 3H), 3.67 (s, 3H), 3.16 (q, J=7.6 Hz, 2H), 1.33 (t, J=7.6 Hz, 3H). LCMS: 325.9 (M+H)+

Workup

concentrationThe mixture was concentrated
customthe residue was purified by silica gel column chromatography (PE/EA=3/1 to 1/2)

Sources & evidence

ORD record: ord-adc72720946147c4a2c42c50d885621e
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034900B2

Reaction notes

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