Potassium Carbonate → Methyl 2'-fluoro-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

HRID 1630989Notes

Reaction equation

HRID 1630989 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14].[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate

Product 1

HCID 58554102Methyl 2'-fluoro-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 4-bromo-3-(methoxymethyl)benzoate (10 g, 38.6 mmol) in toluene (80 mL) and water (20 mL) under nitrogen was added 2-fluorophenylboronic acid (7.0 g, 50.2 mmol), followed by potassium carbonate (16 g, 115.8 mmol) and Pd(PPh3)4 (2.23 g, 1.9 mmol). After 3 hours at 100° C., the reaction mixture was diluted with EtOAc (200 mL) and washed with a saturated aqueous solution of NaHCO3 (100 mL), water (2×100 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by chromatography (silica, pet ether/EtOAc) to afford of the title compound as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.26 (1H, s), 8.04 (1H, d), 7.42 (1H, m), 7.35 (1H, d), 7.14-7.27 (3H, m), 4.34 (2H, s), 3.95 (3H, s), 3.30 (3H, s).

Workup

  1. washwashed with a saturated aqueous solution of NaHCO3 (100 mL), water (2×100 mL) and brine
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by chromatography (silica, pet ether/EtOAc)

Sources & evidence

ORD record
ord-7ba679ebe8d241b29a74b94a90cb4fef
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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