Tetrahydrofuran → 3-(3,5-Difluorophenyl)picolinaldehyde

HRID 250980Notes

Reaction equation

HRID 250980 reaction equation
Br[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.C1COCC1.C([O-])([O-])=O.[Na+].[Na+].[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[C:26]([F:28])[CH:27]=1>COCCOC.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:21][C:22]1[CH:23]=[C:24]([C:2]2[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:25]=[C:26]([F:28])[CH:27]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 164142313-Bromopyridine-2-carbaldehyde

Product 1

HCID 717429023-(3,5-Difluorophenyl)picolinaldehydeYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-bromo-pyridine-2-carbaldehyde (1.2 g, 6.45 mmol) dissolved in ethylene glycol dimethyl ether (25 mL), THF (10 mL) and saturated solution of Na2CO3 (9 mL) was added 3,5 difluorophenyl boronic acid (1.12 g, 7.10 mmol). Purge the mixture with Ar gas (10 min). To this mixture was added Pd(PPh3)4 (373 mg, 0.33 mmol) and stir under a positive pressure of Ar at 90° C. for 16 hours. The reaction mixture was quenched with a solution of saturated NaHCO3 (50 mL). Extract with CH2Cl2 (2×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a light yellow oil. Purification via column chromatography on silica gel (CH2Cl2:MeOH: 80:20, v/v/v) afforded 3-(3,5-difluoro-phenyl)-pyridine-2-carbaldehyde as a white solid (0.86 g, 61%). 1H NMR (CDCl3) δ 6.59 (m, 1H), 6.92 (m, 2H), 7.60 (m, 1H), 7.76 (d, 1H, J=7.5 Hz), 8.88 (d, 1H, J=3.5 Hz), 10.11 (s, 1H).

Workup

  1. customPurge the mixture with Ar gas (10 min)
  2. customThe reaction mixture was quenched with a solution of saturated NaHCO3 (50 mL)
  3. extractionExtract with CH2Cl2 (2×50 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a light yellow oil
  8. customPurification via column chromatography on silica gel (CH2Cl2:MeOH: 80:20, v/v/v)

Sources & evidence

ORD record
ord-a35dd64a074b4a8abc7746b8a7990a24
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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