Sodium Carbonate → HCID 66955591, compound

HRID 2066623Notes

Reaction equation

HRID 2066623 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:22]1[CH:23]=[CH:24][C:25]([F:28])=[N:26][CH:27]=1>C1(C)C=CC=CC=1.CCO.C([O-])(O)=O.[Na+].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]>[F:28][C:25]1[CH:24]=[CH:23][C:22]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=2)=[CH:27][N:26]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 27831685-Bromo-2-fluoropyridine

Product 1

HCID 66955591HCID 66955591, compoundYield 100%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
86.5 °C

Procedure

A stirred mixture of 4-(trifluoromethoxy)phenylboronic acid (1.55 g, 7.53 mmol) and Pd(dppf)Cl2 (367 mg, 0.502 mmol) in toluene (50 mL) and EtOH (25 mL) was degassed for 15 min (vacuum pump) and then N2 was added. An aqueous solution of 2M Na2CO3 (12.5 mL, 25.0 mmol) was added by syringe and the stirred mixture was again degassed for 15 min, and then N2 was added, followed by 5-bromo-2-fluoropyridine (91) (0.53 mL, 5.15 mmol). The resulting mixture was stirred at 85-88° C. for 3 h, and then cooled, diluted with aqueous NaHCO3 (100 mL) and extracted with CH2Cl2 (4×100 mL). The extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-10% CH2Cl2/petroleum ether firstly gave foreruns, and then further elution with 10-20% CH2Cl2/petroleum ether gave 2-fluoro-5-[4-(trifluoromethoxy)phenyl]pyridine (92) (1.32 g, 100%) as a white solid: mp (CH2Cl2/petroleum ether) 58-60° C.; 1H NMR (CDCl3) δ 8.40 (d, J=2.5 Hz, 1H), 7.94 (ddd, J=8.4, 7.6, 2.6 Hz, 1H), 7.55 (dt, J=8.8, 2.5 Hz, 2 ft), 7.33 (br d, J=8.0 Hz, 2H), 7.02 (dd, J=8.5, 3.0 Hz, 1H); HRESIMS calcd for C12H8F4NO m/z (MH+) 258.0537. found 258.0531.

Workup

  1. customwas degassed for 15 min (vacuum pump)
  2. additionN2 was added
  3. customthe stirred mixture was again degassed for 15 min
  4. additionN2 was added
  5. temperaturecooled
  6. extractionextracted with CH2Cl2 (4×100 mL)
  7. customThe extracts were evaporated to dryness
  8. customthe residue was chromatographed on silica gel
  9. washElution with 0-10% CH2Cl2/petroleum ether firstly gave foreruns
  10. washfurther elution with 10-20% CH2Cl2/petroleum ether

Sources & evidence

ORD record
ord-8a98d9382f924bd8aa9f6e955058cecb
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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