Isopropanol → Methyl 2'-fluoro-2-hydroxy-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

HRID 1662543

Reaction equation

HRID 1662543 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1I)[C:5]([O:7][CH3:8])=[O:6].[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1B(O)O.C(O)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[OH:1]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 10378812Methyl 3-hydroxy-4-iodobenzoate

Product 1

HCID 57705807Methyl 2'-fluoro-2-hydroxy-5'-(methyloxy)-1,1'-biphenyl-4-carboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

To a round bottom flask containing 83.26A (1.0938 g, 3.93 mmol) and 2-fluoro-5-methoxyphenylboronic acid (0.7053 g, 4.15 mmol) (commercially available from Aldrich) was added a premixed solution of 1:1 isopropanol (6 mL) and water (6 mL). After stirring at room temperature for 5 minutes, sodium carbonate (0.5526 g, 5.21 mmol) and palladium, 10 wt % on activated carbon (0.0725 g, 0.0681 mmol) were added, and the reaction was then heated to 65° C. After 17 hours, the reaction was cooled to room temperature and then filtered through Celite. The filtrate was concentrated and then saturated aqueous ammonium chloride was added. After extracting three times with EtOAc, the organic solvent was removed under reduced pressure. The residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane) to afford 83.26B (834.3 mg, 77% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.69 (2H, td, J=7.7, 1.7 Hz), 7.33 (1H, d, J=7.8 Hz), 7.14 (1H, t, J=9.0 Hz), 6.94 (1H, dt, J=9.0, 3.5 Hz), 6.89 (1H, dd, J=5.9, 3.2 Hz), 5.42 (1H, s), 3.94 (3H, s), 3.82 (3H, s).

Workup

  1. temperaturethe reaction was then heated to 65° C
  2. waitAfter 17 hours
  3. temperaturethe reaction was cooled to room temperature
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated
  6. additionsaturated aqueous ammonium chloride was added
  7. extractionAfter extracting three times with EtOAc
  8. customthe organic solvent was removed under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-a938543bd074411cbd709b6cc4893b02
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Linked notes

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