Sodium Carbonate → HCID 56604654, compound

HRID 1496925Notes

Reaction equation

HRID 1496925 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][N:20]=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:25][C:22]1[CH:23]=[CH:24][C:19]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=2)=[N:20][CH:21]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 27831712-Bromo-5-fluoropyridine

Product 1

HCID 56604654HCID 56604654, compoundYield 46%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
89 °C

Procedure

A stirred mixture of 4-(hydroxymethyl)phenylboronic acid (34) (501 mg, 3.30 mmol) and Pd(dppf)Cl2 (338 mg, 0.462 mmol) in toluene (36 mL) and EtOH (18 mL) was degassed for 15 min (vacuum pump) and then N2 was added. An aqueous solution of 2M Na2CO3 (9 mL, 18 mmol) was added by syringe and the stirred mixture was again degassed for 15 min, and then N2 was added. 2-Bromo-5-fluoropyridine (110) (1.44 g, 8.18 mmol) was added by syringe and the resulting mixture was stirred at 89° C. for 200 min. The cooled mixture was then diluted with aqueous NaHCO3 (100 mL) and extracted with CH2Cl2 (5×100 mL). The extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with CH2Cl2 and 0-25% Et2O/petroleum ether firstly gave foreruns, and then further elution with 33-50% Et2O/petroleum ether gave [4-(5-fluoro-2-pyridinyl)phenyl]methanol (111) (307 mg, 46%) as a cream solid (following pentane trituration): mp 100-101° C.; 1H NMR (CDCl3) δ 8.54 (d, J=2.9 Hz, 1H), 7.94 (dt, J=8.4, 1.9 Hz, 2H), 7.72 (ddd, J=8.8, 4.2, 0.5 Hz, 1H), 7.50-7.43 (m, 3H), 4.76 (d, J=6.0 Hz, 2H), 1.69 (t, J=6.0 Hz, 1H); HRESIMS calcd for C12H11FNO m/z [M+H]+ 204.0819, found 204.0824.

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. extractionextracted with CH2Cl2 (5×100 mL)
  6. customThe extracts were evaporated to dryness
  7. customthe residue was chromatographed on silica gel
  8. washElution with CH2Cl2 and 0-25% Et2O/petroleum ether firstly gave foreruns
  9. washfurther elution with 33-50% Et2O/petroleum ether

Sources & evidence

ORD record
ord-1dd0a5d6b4174f9a9590308db9fb54c3
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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