Water → Methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate

HRID 850151Notes

Reaction equation

HRID 850151 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[OH-].[Na+].Br[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20]([O:22][CH3:23])=[O:21].O>C1OCCOCCOCCOCCOC1.C1(C)C=CC=CC=1.CN(C=O)C.[I-].[Na+]>[Cl:8][C:4]1[N:3]=[C:2]([O:1][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH:7]=[CH:6][CH:5]=1

Participants

9

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 15168495Benzeneacetic acid, 2-(bromomethyl)-, methyl esterHCID 1785160256-chloropyridin-2-ol

Product 1

HCID 10989960Methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetateYield 61.4%

Reagents, catalysts & solvents 4

HCID 5238Sodium IodideCatalystHCID 3633615-Crown-5CatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-hydroxy6-chloropyridine (0.84 g, 6.5 mmol), sodium hydroxide (0.275 g, 6.9 mmol) and 15-crown-5 (1 drop) in dry toluene (15 ml) were stirred at reflux for 1.5 hours. The toluene was removed under reduced pressure and the white salt residue was dissolved in dry DMF (10 ml). Methyl 2-bromomethylphenylacetate (1.5 g, 6.2 mmol) in dry DMF (10 ml) was added dropwise along with sodium iodide (10 mg). The mixture was stirred at room temperature for 2 hours, poured into water and extracted with diethyl ether. The ether extracts were washed with water, dried and the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane) to give methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate (1.11 g, 61%) (Compound No. 1 in Table 1) as a pale yellow oil; 1H NMR(270 MHz)δ:3.67(3H,s), 3.82(2H,s), 5.39(2H,s) 6.65(1H,d), 6.90(1H,d), 7.25-7.55(5H,m) ppm.

Workup

  1. temperatureat reflux for 1.5 hours
  2. customThe toluene was removed under reduced pressure
  3. dissolutionthe white salt residue was dissolved in dry DMF (10 ml)
  4. stirringThe mixture was stirred at room temperature for 2 hours
  5. extractionextracted with diethyl ether
  6. washThe ether extracts were washed with water
  7. customdried
  8. customthe ether removed in vacuo
  9. customleaving a yellow oil which
  10. customwas purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1056a32c409b4d60a2276609862680a4
Source dataset
uspto-grants-2000_01
Patent number
US06015905

Reaction notes

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