Benzyl Alcohol → Methyl 2-(benzyloxy)-6-chloroisonicotinate

HRID 732466Notes

Reaction equation

HRID 732466 reaction equation
[H-].[Na+].Cl[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([Cl:13])[N:12]=1)[C:7]([OH:9])=[O:8].[CH2:14]([OH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.I[CH2:23]I.[Cl-].[Na+]>CN(C=O)C>[CH3:23][O:9][C:7](=[O:8])[C:6]1[CH:10]=[C:11]([Cl:13])[N:12]=[C:4]([O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:5]=1

Participants

7

Reactant 5

HCID 244Benzyl AlcoholHCID 5234Sodium ChlorideHCID 6346DiiodomethaneHCID 24758Sodium hydrideHCID 948302,6-Dichloroisonicotinic acid

Product 1

HCID 57930944Methyl 2-(benzyloxy)-6-chloroisonicotinateYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add sodium hydride (1.15 g, 28.75 mmol 60% in mineral oil) to a suspension of 2,6-dichloroisonicotinic acid (2 g, 10.42 mmol) at 0° C. in DMF (40 mL). Warm to room temperature and stir for 10 min. Add benzyl alcohol (1.35 mL, 13.045 mmol) dropwise and heat to 80° C. for 1 h. Cool to room temperature, add diiodomethane (2 mL) and stir for 30 min. Pour into saturated aqueous sodium chloride and partition between ethyl acetate and water. Dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes) to give the title compound as a colorless oil (2.3 g, 79%).

Workup

  1. temperatureCool to room temperature
  2. stirringstir for 30 min
  3. custompartition between ethyl acetate and water
  4. dry with materialDry (magnesium sulfate)
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-cd6306c143274409b8d01d17099dd5a7
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

Loading…