Dichloromethane → 3-(Bromomethyl)-2,6-dichloro-5-fluoropyridine

HRID 2224297Notes

Reaction equation

HRID 2224297 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8]O)=[CH:6][C:5]([F:10])=[C:4]([Cl:11])[N:3]=1.P(Br)(Br)[Br:13].C(Cl)Cl.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[Br:13][CH2:8][C:7]1[C:2]([Cl:1])=[N:3][C:4]([Cl:11])=[C:5]([F:10])[CH:6]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24614Phosphorus tribromideHCID 516892Sodium Bicarbonate2×HCID 23114857(2,6-Dichloro-5-fluoropyridin-3-yl)methanol

Product 1

HCID 597175733-(Bromomethyl)-2,6-dichloro-5-fluoropyridineYield 88%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred mixture of alcohol 1A (3.52 g, 17.9 mmol) in CHCl3 (100 mL) under argon was added 1M PBr3 in CH2Cl2 (18.0 mL, 18.0 mmol). The reaction mixture was heated to reflux for 15 minutes, cooled to room temperature, then poured into a mixture of ice and saturated NaHCO3 solution (200 mL). The pH was adjusted to basic by addition of solid NaHCO3. The aqueous layer was extracted with EtOAc. The combined EtOAc extracts were washed with brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 1B (4.11 g, 88%). HPLC Rt=2.78 min. (Column: YMC ODS-A 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 15 minutes
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined EtOAc extracts were washed with brine
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b975a3e73c9418b9cdde909bdfa9d51
Source dataset
uspto-grants-2008_05
Patent number
US07378426B2

Reaction notes

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