Benzyl Bromide → 3-(Benzyloxy)-5-bromo-2-chloropyridine

HRID 625937Notes

Reaction equation

HRID 625937 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[C:5]([Cl:8])=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.O>[CH2:16]([O:9][C:4]1[C:5]([Cl:8])=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 167481065-Bromo-2-chloropyridin-3-ol

Product 1

HCID 226075323-(Benzyloxy)-5-bromo-2-chloropyridineYield 94.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Bromo-2-chloro-pyridin-3-ol (500 mg, 2.399 mmol) and Cs2CO3 (1.2 g, 3.68 mmol) were combined in DMF (10 mL) at RT. To this was added benzyl bromide (0.34 mL, 2.86 mmol). After stirring overnight the mixture was diluted with H2O and extracted with Et2O (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated. Flash column (Biotage-SNAP-50 g, 0-10% EtOAc/hexanes) gave the title compound (674 mg, 94%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 8.07 (d, J=2.0 Hz, 1 H); 7.53-7.35 (m, 6 H); 5.16 (s, 2 H). LC/MS (M+H)+ 298/300/302.

Workup

  1. extractionextracted with Et2O (3×)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-9fc30344cf3f4bb4898d832b3a15b407
Source dataset
uspto-grants-2016_04
Patent number
US09309199B2

Reaction notes

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