2-Fluoro-3-methoxyphenylboronic acid → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(2-fluoro-3-methoxyphenyl)-5-ethoxycarbonyl-4-pyridone

HRID 495522Notes

Reaction equation

HRID 495522 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:8](=[O:17])[C:7](Br)=[C:6]1[CH3:19].[F:25][C:26]1[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.[OH-].[Ba+2].[OH-]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC=CC=1.C(O)C.COCCOC>[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:8](=[O:17])[C:7]([C:27]2[CH:28]=[CH:29][CH:30]=[C:31]([O:32][CH3:33])[C:26]=2[F:25])=[C:6]1[CH3:19]

Participants

6

Reactant 3

HCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 6093286Barium hydroxideHCID 223272271-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone

Product 1

HCID 223272391-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(2-fluoro-3-methoxyphenyl)-5-ethoxycarbonyl-4-pyridone

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 86588578Benzene ethanol 1,2-dimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone (1.5 g, 3.7 mmol) was evacuated in a pressure vessel with 2-fluoro-3-methoxyphenyl boronic acid (764 mg, 4.5 mmol) and tetrakis(triphenylphosphine) palladium (0) (428 mg, 370 μmol). A mixture of benzene/ethanol/1,2-dimethoxyethane (74 ml in a 10/1/11 ratio) and barium hydroxide (saturated aqueous, about 0.5M) was then added under vacuum, the vessel sealed under N2, and the reaction stirred at 90° C. for twelve hours, protected from light. The organic layer was concentrated and purified using flash silica chromatography (EtOAc/hexanes-1/4 to MeOH/CH2Cl2-2/98), with the product eluting as the third spot. The product was dried as an amber oil (1.12 g, 2.5 mmol, 68%). 1H NMR (CDCl3, 300 MHz) δ 6.80-7.80 (m, 6H), 5.29 (s, 2H), 4.37-4.33 (m, 2H), 3.87 (s, 3H), 3.38 (s, 3H), 2.26 (s, 3H), 1.35 (t, 3H); LCMS=446 (MH+).

Workup

  1. additionwas then added under vacuum
  2. customthe vessel sealed under N2
  3. concentrationThe organic layer was concentrated
  4. custompurified
  5. washwith the product eluting as the third spot

Sources & evidence

ORD record
ord-cb613d474c1244ab84f3549f06c19176
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

Loading…