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

HRID 518547Notes

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-4a5c68b1b18b4cf6832cf46d7131a502
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115114B2

Reaction notes

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